Triethylamine → (3R*,4S*)-3-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-4-[(methyl-phenylmethanesulfonyl-amino)-methyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1158491노트

반응식

HRID 1158491 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][NH:14][CH3:15])[C@H:10]([CH2:16][N:17]([CH:34]([CH3:36])[CH3:35])[C:18](=[O:33])[C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH2:28][CH2:29][CH2:30][O:31][CH3:32])[CH:20]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:37]1([CH2:43][S:44](Cl)(=[O:46])=[O:45])[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.C(N(CC)CC)C.C([O-])(O)=O.[Na+]>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH3:15])[S:44]([CH2:43][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)(=[O:46])=[O:45])[C@H:10]([CH2:16][N:17]([CH:34]([CH3:36])[CH3:35])[C:18](=[O:33])[C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH2:28][CH2:29][CH2:30][O:31][CH3:32])[CH:20]=2)[CH2:9]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

참가 물질

6

반응물 4

HCID 8471TriethylamineHCID 74740Phenylmethanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 59512501(3R*,4R*)-3-({Isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-4-methylaminomethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 68643106(3R*,4S*)-3-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-4-[(methyl-phenylmethanesulfonyl-amino)-methyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a solution of (3R*,4R*)-3-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-4-methylaminomethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (89 mg, 0.175 mmol) in CH2Cl2 (3 mL), alpha-toluenesulfonyl chloride (40 mg, 0.21 mmol) and triethylamine (30 μL, 0.21 mmol) are added under N2 atmosphere. The mixture is stirred overnight at RT, diluted with CH2Cl2 and poured into an aqueous saturated solution of NaHCO3. The organic layer is separated, and the aqueous one is extracted twice with CH2Cl2. The combined organic extracts are dried over Na2SO4, filtered and concentrated. The crude product is purified by preparative HPLC (C18-ODB-AQ, 5 μm, 20×50 mm, YMC, eluent: CH3CN /H2O+0.1% HCOOH flow: 20 mL/min). The HPLC fractions are collected, and the resulting solution is lyophilized to afford the title product. TLC, Rf (CH2Cl2/MeOH 95:5)=0.3. tR (HPLC, Nucleosil C18 column, 10-100% CH3CN/H2O/5 min, 100% CH3CN/3 min, CH3CN and H2O containing 0.1% TFA, flow: 1.5 ml/min): 5.81 min.

후처리

  1. customThe organic layer is separated
  2. extractionthe aqueous one is extracted twice with CH2Cl2
  3. dry with materialThe combined organic extracts are dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product is purified by preparative HPLC (C18-ODB-AQ, 5 μm, 20×50 mm, YMC, eluent: CH3CN /H2O+0.1% HCOOH flow: 20 mL/min)
  7. customThe HPLC fractions are collected

출처 및 근거

ORD 기록
ord-7f1261c2608f4fdc915795ccd3d2e524
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07807709B2

반응 노트

불러오는 중…