Day: September 7, 2020

19132-06-0 A common heterocyclic compound, 19132-06-0,(2S,3S)-Butane-2,3-diol, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.

To a 500-mL, 3-necked-RBF (equipped with a H20-cooled refluxcondenser and an HC1 trap) was added (2s,3s)-(+)-2,3-butanediol (Aldrich; 15.00mL, 166 mmol) and CC14 (120 mL). SOC12, reagentplus (14.57 mL, 200 mmol)was then added drop wise via a syringe over a period of 20 mm and the resultingmixture was heated to 98C for 45 mm, then allowed to cool to rt. The reactionmixture was then cooled in an ice/H20 bath, MeCN (120 mL) and H20 (150 mL) were added followed by ruthenium(III) chloride (0.035 g, 0.166 mmol). Sodium periodate (53.4 g, 250 mmol) was then added slowly portion wise over 30 mm. The resulting biphasic brown mixture was stirred vigorously while allowed toreach rt for a period of 1.5 h (internal temperature never increased above rt). TLC (50% EtOAc in heptanes) showed complete conversion. The cmde mixture was then poured into ice H20 and extracted twice with 300 mL of Et20. The combined organic layers were washed once with 200 mL of sat. sodium bicarbonate, washed once with 200 mL of brine, dried over Na2504, andconcentrated by rotary evaporation to give (45,55)-4,5-dimethyl-1,3,2- dioxathiolane 2,2-dioxide (21.2 g, 139 mmol) as a red oil.

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,(2S,3S)-Butane-2,3-diol,19132-06-0,its application will become more common.

Reference£º
Patent; AMGEN INC.; HARRINGTON, Paul E.; ASHTON, Kate; BROWN, Sean P.; KALLER, Matthew R.; KOHN, Todd J.; LANMAN, Brian Alan; LI, Kexue; LI, Yunxiao; LOW, Jonathan D.; MINATTI, Ana Elena; PICKRELL, Alexander J.; STEC, Markian M.; TAYGERLY, Joshua; (991 pag.)WO2018/183418; (2018); A1;,
Synthesis and Crystal Structure of a Chiral?C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis
Chiral lanthanide(III) complexes of sulphur¨Cnitrogen¨Coxygen ligand derived from aminothiourea and sodium?D-camphor-¦Â-sulfonate

4254-15-3 A common heterocyclic compound, 4254-15-3,(S)-Propane-1,2-diol, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.

To separate the propylene glycol enantiomers on a chiral gas chromatography column, they were derivatized with acetic anhydride to the methyl esters. Into a small vial equipped with a Teflon lined stir bar was added 1 mL diethyl ether and equal amounts (5-10 drops) propylene glycol, pyridine, and acetic anhydride. The reaction mixture was stirred 3 hours at room temperature, washed with deionized 0 (3 x 1 mL) and dried over Na2S04. The derivatized product was then analyzed via gas chromatography. The diacetate was obtained with an ee of 97percent when (R,i?)-(Cl-salcy)CoN03 was used, and with an ee of 96percent when (5,S)-(Cl-salcy)CoN03 was used, indicating that both enantiomers produced highly regioregular poly(propylene succinate).

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,4254-15-3,(S)-Propane-1,2-diol,its application will become more common.

Reference£º
Patent; CORNELL UNIVERSITY; COATES, Geoffrey; WHITEHEAD, Julie; (60 pag.)WO2016/25675; (2016); A1;,
Synthesis and Crystal Structure of a Chiral?C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis
Chiral lanthanide(III) complexes of sulphur¨Cnitrogen¨Coxygen ligand derived from aminothiourea and sodium?D-camphor-¦Â-sulfonate

A common heterocyclic compound, 19132-06-0,(2S,3S)-Butane-2,3-diol, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route. 19132-06-0

To a 500-mL, 3-necked round-bottomed flask (equipped with a water- cooled reflux condenser and an HCI trap) was added (2s,3s)-(-f-)-2.3-butanediol (Aldrich, Milwaukee Wisconsin)(1500 nil, 166 mniol) and CCI4 (120 ml). Thionyl chloride. reagentplus (14.57 ml, 200 mmoi) was then added drop wise viaa syringe over a period of 20 minutes and the resulting mixture was heated to98 C for 45 minutes, then it was allowed to cool to room temperature. Rf ofintermediate == 0.42 eluting with 50% EtOAc in heptanes; use KMNO4 to visualizecompound, The reaction mixture was then cooled in an ice-water bath. MeCN(120 mL) and water (150 rnL) were added followed by ruthenium(111) chloride(0.035g. 0.166 nunol). Sodium periodate (53.4 g, 250 rnmol) was then addedslowly portion wise over 30 minutes. The resulting biphasic brown mixture was stirred vigorously whie allowed to reach room temperature for a period of 1.5 hour (internal temperature never increased above room temperature). TLC (50% EtOAc in heptanes) showed complete conversion. The crude mixture was thenpoured into ice water and extracted twice with 300 ml of diethyl ether. The combined organic layers were washed once with 200 ml of saturated sodium bicarbonate, washed once with 200 nil of brine, dried over sodium sulfate and concentrated by rotary evaporation to give (4S.5 S)-4,5-dimethyi- 1,3,2- dioxathiolane 2,2-dioxide (21.2 g, 139 mmoi) as a red oil.

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,(2S,3S)-Butane-2,3-diol,19132-06-0,its application will become more common.

Reference£º
Patent; AMGEN INC.; BROWN, Sean P.; BEDKE, David Karl; DEGRAFFENREID, Michael R.; FU, Jiasheng; LI, Zhihong; GONZALEZ LOPEZ DE TURISO, Felix; GONZALEZ BUENROSTRO, Ana; GRIBBLE, Jr., Michael W.; JOHNSON, Michael G.; KOHN, Todd J.; LI, Kexue; LI, Yunxiao; LIZARZABURU, Mike Elias; REW, Yosup; TAYGERLY, Joshua; WANG, Yingcai; YAN, Xuelei; YU, Ming; ZHU, Jiang; ZANCANELLA, Manuel; JIAO, Xian Yun; ZHU, Liusheng; WANG, Xianghong; MEDINA, Julio C.; DUQUETTE, Jason A.; HOUZE, Jonathan B.; VIMOLRATANA, Marc; CARDOZO, Mario G.; CHENG, Alan C.; (2426 pag.)WO2017/147410; (2017); A1;,
Synthesis and Crystal Structure of a Chiral?C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis
Chiral lanthanide(III) complexes of sulphur¨Cnitrogen¨Coxygen ligand derived from aminothiourea and sodium?D-camphor-¦Â-sulfonate

A common heterocyclic compound, 24621-61-2,(S)-Butane-1,3-diol, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route. 24621-61-2

Example 7A (2S)-4-((tert-butyl(dimethyl)silyl)oxy)-2-butanol A 0 C. solution of (S)-(+)-1,3-butanediol (2.1 g, 23.3 mmol), imidazole (1.74 g, 25.6 mmol), and N,N-dimethylformamide (1.0 mL) in dichloromethane (40 mL) was treated with tert-butyl-dimethylsilyl chloride (3.68 g, 23.3 mmol). The reaction mixture was warmed to room temperature, stirred overnight, quenched with saturated aqueous ammonium chloride and extracted with dichloromethane. The combined dichloromethane layers were dried (MgSO4), filtered and concentrated to afford of the desired product of sufficient purity for subsequent use without further purification in near quantitative yield. MS (DCI/NH3) m/z 205 (M+H)+; 1H NMR (300 MHz, CDCl3) delta3.95 (m, 1H), 3.79 (m, 2H), 3.27 (br s, 1H), 1.56 (m 2H), 1.11 (d, 3H), 0.82 (s, 9H), 0.016 (s, 6H).

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,24621-61-2,(S)-Butane-1,3-diol,its application will become more common.

Reference£º
Patent; Bennani, Youssef L.; Black, Lawrence A.; Dwight, Wesley J.; Faghih, Ramin; Gentles, Robert G.; Liu, Huaqing; Phelan, Kathleen M.; Vasudevan, Anil; Zhang, Henry Q.; US2001/49367; (2001); A1;,
Synthesis and Crystal Structure of a Chiral?C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis
Chiral lanthanide(III) complexes of sulphur¨Cnitrogen¨Coxygen ligand derived from aminothiourea and sodium?D-camphor-¦Â-sulfonate

A common heterocyclic compound, 4254-15-3,(S)-Propane-1,2-diol, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route. 4254-15-3

Example 29; N-r(2Z)-3-butviri.31thiazolor4.5-clpyridin-2(3H)-ylidenel-2-(r(2S)-2-hvdroxypropylloxyl-5 -(trifluoromethyl)benzamide; (S)-propane-l,2-diol (52 mg, 0.68 mmol) in THF (1 mL) was treated with NaH (60percent dispersion; 27 mg, 0.68 mmol) at room temperature for 20 minutes. The mixture was cooled to O0C and a solution of Example 2OB (90 mg, 0.23 mmol) in THF (1 mL) was added. The mixture was allowed to warm to room temperature, and stirred for 4 hours. The mixture was diluted with saturated aqueous NaHCO3 (20 mL) and extracted with ethyl acetate (2 x 30 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified by column chromatography using an Analogix.(R). Intellifiash280 .(TM). (SiO2, 0-100 percent ethyl acetate in hexanes) to afford 19 mg (19percent) of the title compound. 1H NMR (500 MHz, CDCl3) delta ppm 1.04 (t, J=7.48 Hz, 3 H) 1.28 (d, J=6.41 Hz, 3 H) 1.47 – 1.59 (m, 2 H) 1.88 – 1.98 (m, 2 H) 3.87 (t, J=8.85 Hz, 1 H) 4.21 – 4.31 (m, 1 H) 4.35 (dd, J=9.15, 2.75 Hz, 1 H) 4.51 – 4.59 (m, 2 H) 7.12 (d, J=8.85 Hz, 1 H) 7.72 (dd, J=8.54, 2.14 Hz, 2 H) 8.51 (d, J=I.83 Hz, 2 H) 8.75 (s, 1 H); MS (DCI/NH3) m/z 454 (M+H)+.

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,(S)-Propane-1,2-diol,4254-15-3,its application will become more common.

Reference£º
Patent; ABBOTT LABORATORIES; FROST, Jennifer, M.; LATSHAW, Steven, P.; DART, Michael, J.; CARROLL, William, A.; PEREZ-MEDRANO, Arturo; KOLASA, Teodozyj; PATEL, Meena; NELSON, Derek, W.; LI, Tongmei; PEDDI, Sridhar; WANG, Xueqing; LUI, Bo; WO2010/71783; (2010); A1;,
Synthesis and Crystal Structure of a Chiral?C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis
Chiral lanthanide(III) complexes of sulphur¨Cnitrogen¨Coxygen ligand derived from aminothiourea and sodium?D-camphor-¦Â-sulfonate

A common heterocyclic compound, 19132-06-0,(2S,3S)-Butane-2,3-diol, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route. 19132-06-0

To a 500-mL, 3-necked-RBF (equipped with a H20-cooled refluxcondenser and an HC1 trap) was added (2s,3s)-(+)-2,3-butanediol (Aldrich; 15.00mL, 166 mmol) and CC14 (120 mL). SOC12, reagentplus (14.57 mL, 200 mmol)was then added drop wise via a syringe over a period of 20 mm and the resultingmixture was heated to 98C for 45 mm, then allowed to cool to rt. The reactionmixture was then cooled in an ice/H20 bath, MeCN (120 mL) and H20 (150 mL) were added followed by ruthenium(III) chloride (0.035 g, 0.166 mmol). Sodium periodate (53.4 g, 250 mmol) was then added slowly portion wise over 30 mm. The resulting biphasic brown mixture was stirred vigorously while allowed toreach rt for a period of 1.5 h (internal temperature never increased above rt). TLC (50% EtOAc in heptanes) showed complete conversion. The cmde mixture was then poured into ice H20 and extracted twice with 300 mL of Et20. The combined organic layers were washed once with 200 mL of sat. sodium bicarbonate, washed once with 200 mL of brine, dried over Na2504, andconcentrated by rotary evaporation to give (45,55)-4,5-dimethyl-1,3,2- dioxathiolane 2,2-dioxide (21.2 g, 139 mmol) as a red oil.

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,19132-06-0,(2S,3S)-Butane-2,3-diol,its application will become more common.

Reference£º
Patent; AMGEN INC.; HARRINGTON, Paul E.; ASHTON, Kate; BROWN, Sean P.; KALLER, Matthew R.; KOHN, Todd J.; LANMAN, Brian Alan; LI, Kexue; LI, Yunxiao; LOW, Jonathan D.; MINATTI, Ana Elena; PICKRELL, Alexander J.; STEC, Markian M.; TAYGERLY, Joshua; (991 pag.)WO2018/183418; (2018); A1;,
Synthesis and Crystal Structure of a Chiral?C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis
Chiral lanthanide(III) complexes of sulphur¨Cnitrogen¨Coxygen ligand derived from aminothiourea and sodium?D-camphor-¦Â-sulfonate

A common heterocyclic compound, 4254-15-3,(S)-Propane-1,2-diol, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route. 4254-15-3

To separate the propylene glycol enantiomers on a chiral gas chromatography column, they were derivatized with acetic anhydride to the methyl esters. Into a small vial equipped with a Teflon lined stir bar was added 1 mL diethyl ether and equal amounts (5-10 drops) propylene glycol, pyridine, and acetic anhydride. The reaction mixture was stirred 3 hours at room temperature, washed with deionized 0 (3 x 1 mL) and dried over Na2S04. The derivatized product was then analyzed via gas chromatography. The diacetate was obtained with an ee of 97percent when (R,i?)-(Cl-salcy)CoN03 was used, and with an ee of 96percent when (5,S)-(Cl-salcy)CoN03 was used, indicating that both enantiomers produced highly regioregular poly(propylene succinate).

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,(S)-Propane-1,2-diol,4254-15-3,its application will become more common.

Reference£º
Patent; CORNELL UNIVERSITY; COATES, Geoffrey; WHITEHEAD, Julie; (60 pag.)WO2016/25675; (2016); A1;,
Synthesis and Crystal Structure of a Chiral?C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis
Chiral lanthanide(III) complexes of sulphur¨Cnitrogen¨Coxygen ligand derived from aminothiourea and sodium?D-camphor-¦Â-sulfonate

A common heterocyclic compound, 24621-61-2,(S)-Butane-1,3-diol, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route. 24621-61-2

(Example 5-1) Under ice cooling, to a dichloromethane solution (20.0 ml) of (S)-1,3-butanediol (519 mg) were added triethylamine (1.04 ml) and tert-butylchlorodiphenylsilane (1.63 ml), followed by stirring at room temperature overnight. The reaction solution was poured into a saturated aqueous ammonium chloride solution, and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography to afford (2S)-4-{[tert-butyl(diphenyl)silyl]oxy}butan-2-ol (1.69 g). 1H NMR(400 MHz,CDCl3) delta: 1.05 (9H, s), 1.22 (3H, d, J = 6.3 Hz), 1.58-1.68 (1H, m), 1.69-1.81 (1H, m), 3.31 (1H, d, J = 2.0 Hz), 3.80-3.91 (2H, m), 4.07-4.15 (1H, m), 7.37-7.50 (6H, m), 7.69 (4H, d, J = 6.2 Hz).

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,24621-61-2,(S)-Butane-1,3-diol,its application will become more common.

Reference£º
Patent; Daiichi Sankyo Company, Limited; EP2471792; (2012); A1;,
Synthesis and Crystal Structure of a Chiral?C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis
Chiral lanthanide(III) complexes of sulphur¨Cnitrogen¨Coxygen ligand derived from aminothiourea and sodium?D-camphor-¦Â-sulfonate

A common heterocyclic compound, 24621-61-2,(S)-Butane-1,3-diol, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route. 24621-61-2

Example 1 Preparation of (3S)-1-p-Toluenesulfonyloxy-3-triethylsilyloxy-butane (2)To a stirred solution of the (S)-(+)-1,3-butanediol 1 (1 g, 11.1 mmol), DMAP (30 mg, 0.25 mmol) and Et3N (4.6 mL, 3.33 g, 33 mmol) in anhydrous methylene chloride (20 mL) p-toluenesulfonyl chloride (2.54 g, 13.3 mmol) was added at 0 C. The reaction mixture was stirred at 4 C. for 22 h. Methylene chloride was added and the mixture was washed with water, dried (Na2SO4) and concentrated under reduced pressure. A residue was chromatographed on silica gel with hexane/ethyl acetate (8:2, then 1:1) to afford the tosylate (2.31 g, 85% yield) as a colorless oil.To a stirred solution of the tosylate (2.31 g, 9.5 mmol) and 2,6-lutidine (1.2 mL, 1.12 g, 10.5 mmol) in anhydrous methylene chloride (15 mL) triethylsilyl trifluoromethanesulfonate (2.1 mL, 2.51 g, 9.5 mmol) was added at -50 C. The reaction mixture was allowed to warm to room temperature (4 h) and stirring was continued for additional 20 h. Methylene chloride was added and the mixture was washed with water, dried (Na2SO4) and concentrated under reduced pressure. A residue was chromatographed on silica gel with hexane/ethyl acetate (97:3) to afford the product 2 (2.71 g, 80% yield) as a colorless oil:[alpha]D+18.0 (c 2.38, CHCl3); 1H NMR (400 MHz, CDCl3) delta 7.77 (2H, d, J=8.2 Hz, o-HTs), 7.33 (2H, d, J=8.2 Hz, m-HTs), 4.10 (2H, t, J=6.1 Hz, 1-H2), 3.90 (1H, m, 3-H), 2.43 (3H, s, MeTs), 1.72 (2H, m, 2-H2), 1.10 (3H, d, J=6.2 Hz, 4-H3), 0.88 (9H, t, J=8.0 Hz, 3¡ÁSiCH2CH3), 0.50 (6H, q, J=8.0 Hz, 3¡ÁSiCH2CH3); 13C NMR (100 MHz) delta 144.62 (s, p-CTs), 133.03 (s, i-CTs), 129.72 (d, m-CTs), 127.82 (d, o-CTs), 67.78 (t, C-1), 64.46 (d, C-3), 38.47 (t, C-2), 23.82 (q, C-4), 21.52 (q, MeTs), 6.71 (q, SiCH2CH3), 4.77 (t, SiCH2CH3); MS (EI) m/z 359 (5, MH+), 329 (87, M+-C2H5), 259 (100), 233 (54), 197 (50), 179 (74), 163 (40), 149 (48), 135 (38), 115 (53), 91 (71); exact mass calculated for C15H25O4SSi (M+-C2H5) 329.1243, found 329.1239.

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,(S)-Butane-1,3-diol,24621-61-2,its application will become more common.

Reference£º
Patent; DeLuca, Hector F.; Clagett-Dame, Margaret; Plum, Lori A.; Chiellini, Grazia; Grzywacz, Pawel; US2009/170821; (2009); A1;,
Synthesis and Crystal Structure of a Chiral?C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis
Chiral lanthanide(III) complexes of sulphur¨Cnitrogen¨Coxygen ligand derived from aminothiourea and sodium?D-camphor-¦Â-sulfonate

4254-15-3 A common heterocyclic compound, 4254-15-3,(S)-Propane-1,2-diol, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.

Example 33 : (2R, 75R)-2-[(l-Aminoisoquinolin-6-yl)amino]-8-fluoro-7- {[(25)-l- hydroxypropan-2-yl]oxy } -4, 15,20-trimethyl- 13 -oxa-4, 1 1- diazatricyclo[14.2.2.16, 10]henicosa-l(18),6,8, 10(21), 16, 19-hexaene-3, 12-dione; trifluoroacetic acid [00356] To a solution of (s)-(+)-l,2-propanediol (2.0 g, 26.3 mmol) in DMF (5 mL) was added TBS-C1 (5.94 g, 39.4 mmol) and imidazole (2.147 g, 31.5 mmol). The reaction was stirred at 25 ¡ãC for 18 h. The reaction mixture was partitioned between ethyl acetate and sat. ammonium chloride. The organic phase was washed with sat. ammonium chloride and brine, dried (MgS04) and concentrated in vacuo. The crude product was purified by flash chromatography to give 33A (4.0 g, 80percent yield) as a colorless oil. 33B: (5)-Benzyl 2-((l-((tert-butyldimethylsilyl)oxy)propan-2-yl)oxy)-3-fluoro-5- nitrobenzyl(methyl)carbamate [00357] To a solution of 27B (400 mg, 1.197 mmol), 33A (251 mg, 1.316 mmol) and triphenylphosphine (345 mg, 1.316 mmol) in THF (10 mL) at 0 ¡ãC, was added DIAD (0.256 mL, 1.316 mmol) dropwise. The reaction mixture was allowed to slowly warm to rt and stirred for 16 h, then was concentrated. The crude product was purified by flash chromatography (0 to 40percent ethyl acetate/hexanes) to give 33B (577 mg, 1.139 mmol, 95percent yield) as colorless oil. MS (ESI) m/z: 507.1 [M+1]+. H MR (400 MHz, chloroform-d) delta ppm 7.78 – 7.94 (2 H, m) 7.27 – 7.43 (5 H, m) 5.17 (2 H, d, J=20.1 Hz) 4.46 – 4.74 (3 H, m) 3.65 – 3.81 (2 H, m) 2.97 (3 H, d, J=15.8 Hz) 1.31 (3 H, t, J=7.0 Hz) 0.81 (9 H, d, J=7.0 Hz) -0.05 – 0.04 (6 H, m) rotamers. 33C: (S)-4-((l-((tert-Butyldimethylsilyl)oxy)propan-2-yl)oxy)-3-fluoro-5- ((methylamino)methyl)aniline [00358] To a degassed solution of 33B (573 mg, 1.131 mmol) in MeOH (10 mL), was added 10percent Pd-C (50 mg, 0.047 mmol). The mixture was evacuated and flushed with H2 (3X), then was stirred under an atmosphere of H2 for 8 h. The mixture was filtered and concentrated to give 33C (382 mg, 1.115 mmol, 99percent yield) as a pale brown oil. MS (ESI) m/z: 343.1 [M+l]+. PI MR (400 MHz, chloroform-d) delta ppm 6.40 (1 H, d, J=1.8 Hz) 6.33 (1 H, dd, J=12.5, 2.8 Hz) 4.20 (1 H, sxt, J=5.7 Hz) 3.62 – 3.79 (4 H, m) 3.53 (2 H, br. s.) 2.40 (3 H, s) 1.25 (3 H, d, J=6.3 Hz) 0.89 (9 H, s) 0.05 (6 H, s). 33D: tert-Butyl N- {6-[({[(5-amino-2- { [(25)- l-[(tert-butyldimethylsilyl)oxy]propan-2- yl]oxy } -3 -fluorophenyl)methyl](methyl)carbamoyl} ( {4-[(2R)- 1 -hydroxypropan-2-yl]-3 – methylphenyl} )methyl)amino]isoquinolin- 1 -yl} -N-[(tert-butoxy)carbonyl]carbamate [00359] To Intermediate 5 (100 mg, 0.515 mmol), Intermediate 1 (185 mg, 0.515 mmol), and glyoxylic acid monohydrate (47.4 mg, 0.515 mmol), were added DMF (6.00 mL) and acetonitrile (6 mL). The mixture was stirred at 80 ¡ãC for 1 h, then was cooled to rt. To the mixture were added sequentially 33C (201 mg, 0.587 mmol), DMF (6.00 mL), TEA (0.215 mL, 1.546 mmol) and BOP (251 mg, 0.567 mmol). The reaction mixture was stirred at rt for 1 h, then was diluted with H20 and extracted with EtOAc (3X). The extract was washed with brine, dried ( a2S04) and concentrated. The crude product was purified by flash chromatography (1 to 15percent MeOH/methylene chloride) to give 33D (422 mg, 0.474 mmol, 92percent yield) as an orange foam. MS (ESI) m/z: 890.3 [M+l]+. H MR: complicated due to presence of diastereomers and amide rotamers. Example 33 [00360] To a solution of 33D (417 mg, 0.468 mmol) in dichloromethane (10 mL) and acetonitrile (5 mL) at 0 ¡ãC, was added phosgene (20percent in toluene, 0.243 mL, 0.492 mmol) dropwise. The mixture was stirred at 0 ¡ãC for 20 min, then was removed from the cooling bath and bubbled with Ar for 20 min. This mixture was added dropwise via a syringe pump into a solution of TEA (0.392 mL, 2.81 mmol) in dichloromethane (190 mL) over 5 h. The reaction mixture was allowed to stir at rt for 11 h, and then concentrated. The crude product was purified by flash chromatography (1 to 15percent MeOH/methylene chloride) to give a mixture of diastereoisomers. The diastereomers were separated by a prep chiral HPLC (R,R-Whelk-0 column 21.1 x 250 mm). The desired fractions were combined and concentrated. The residue was treated with TFA (4 mL) for 15 min. The reaction mixture was concentrated and purified by prep HPLC to give Example 33 (52.9 mg, 0.074 mmol, 31.4percent yield) white solid. MS (ESI) m/z: 602.2 [M+l]+. NMR (400 MHz, methanol-d4) delta ppm 8.05 (1 H, d, J=9.3 Hz) 7.64 (1 H, dd, J=7.8, 1.8 Hz) 7.44 (1 H, d, J=7.8 Hz) 7.31 (1 H, d, J=7.0 Hz) 7.18 – 7.23 (2 H, m) 6.91 (1 H, d, J=7.3 Hz) 6.83 (1 H, d, J=2.3 Hz) 6.53 (1 H, dd, J=12.4, 2.4 Hz) 5.73 (1 H, s) 5.66 (1 H, br. s.) 5.37 (1 H, d, J=17.1 Hz) 4.65 (1 H, t, J=11.0 Hz) 4.27 – 4.38 (1 H, m, J=5.7, 5.7, 5.7, 5.7, 5.4 Hz) 4.06 (1 H, d, J=17.3 Hz) 3.96 (1 H, dd, J=10.8, 4.3 Hz) 3.63 (2 H, d, J=4.8 Hz) 3.43 – 3.55 (1 H, m) 3.27 (3 H, s) 2.34 (3 H, s) 1.30 (3 H, d, J=7.0 Hz) 1.27 (3 H, d, J=6.3 Hz). Analytical HPLC (low pH, 254 nM): Sunfir…

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,4254-15-3,(S)-Propane-1,2-diol,its application will become more common.

Reference£º
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Synthesis and Crystal Structure of a Chiral?C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis
Chiral lanthanide(III) complexes of sulphur¨Cnitrogen¨Coxygen ligand derived from aminothiourea and sodium?D-camphor-¦Â-sulfonate