1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-(S)-[(5-Chloro-1H-pyrrolo[2,3-b]pyridine-2-carbonyl)amino]-3-(4-fluorophenyl)-propionic acid tert-butyl ester

HRID 1693485노트

반응식

HRID 1693485 반응식
[Cl:1][C:2]1[CH:3]=[C:4]2[CH:10]=[C:9]([C:11]([OH:13])=O)[NH:8][C:5]2=[N:6][CH:7]=1.Cl.[C:15]([O:19][C:20](=[O:31])[C@@H:21]([NH2:30])[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1)([CH3:18])([CH3:17])[CH3:16].C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C>CN(C=O)C>[C:15]([O:19][C:20](=[O:31])[C@@H:21]([NH:30][C:11]([C:9]1[NH:8][C:5]2=[N:6][CH:7]=[C:2]([Cl:1])[CH:3]=[C:4]2[CH:10]=1)=[O:13])[CH2:22][C:23]1[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=1)([CH3:18])([CH3:16])[CH3:17]

참가 물질

7

반응물 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 446307055-chloro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acidHCID 67278629tert-butyl (2S)-2-amino-3-(4-fluorophenyl)propanoate hydrochloride

생성물 1

HCID 597535552-(S)-[(5-Chloro-1H-pyrrolo[2,3-b]pyridine-2-carbonyl)amino]-3-(4-fluorophenyl)-propionic acid tert-butyl ester

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of 5-chloro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid (Preparation 57, 500 mg, 2.54 mmol) in DMF (20 mL) was added 2-(S)-amino-3-(4-fluorophenyl)propionic acid tert-butyl ester hydrochloride (Preparation 114, 701 mg, 2.54 mmol), HOBt (344 mg, 2.54 mmol) and DIPEA (1.4 mL, 7.88 mmol). After 5 min, EDCI (634 mg, 3.31 mmol) was added and the reaction mixture stirred at rt for 72 h. The solvent was removed in vacuo and the solid partitioned between water (50 mL) and ethyl acetate (3×40 mL). The combined organic phase was washed with brine (20 mL), dried (MgSO4), concentrated in vacuo and purified by chromatography on silica gel eluting with methanol:dichloromethane (1:99) to give the title compound. δH (CD3OD): 1.42 (9H, s), 3.09 (1H, dd), 3.22 (1H, dd), 4.76 (1H, m), 6.98 (2H, m), 7.07 (1H, s), 7.27 (2H, m), 8.06 (1H, d), 8.28 (1H, d); m/z (ES+)=418 [M+H]+.

후처리

  1. customThe solvent was removed in vacuo
  2. customthe solid partitioned between water (50 mL) and ethyl acetate (3×40 mL)
  3. washThe combined organic phase was washed with brine (20 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. custompurified by chromatography on silica gel eluting with methanol:dichloromethane (1:99)

출처 및 근거

ORD 기록
ord-145e1bbb1950479cb01c002bc0cb3b71
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08158622B2

반응 노트

불러오는 중…