Potassium Iodide → (2R,5S)-4-{2-[6-(4-Fluoro-benzyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridin-1-yl]-2-oxo-ethyl}-2-methyl-5-((R)-3-methyl-morpholin-4-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 1475521노트

반응식

HRID 1475521 반응식
Cl.Cl[CH2:3][C:4]([N:6]1[C:14]2[C:9](=[N:10][CH:11]=[C:12]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[CH:13]=2)[C:8]([CH3:24])([CH3:23])[CH2:7]1)=[O:5].[C:25]([O:29][C:30]([N:32]1[CH2:37][C@H:36]([CH2:38][N:39]2[CH2:44][CH2:43][O:42][CH2:41][C@H:40]2[CH3:45])[NH:35][CH2:34][C@H:33]1[CH3:46])=[O:31])([CH3:28])([CH3:27])[CH3:26].C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>C(#N)C.O>[C:25]([O:29][C:30]([N:32]1[CH2:37][C@H:36]([CH2:38][N:39]2[CH2:44][CH2:43][O:42][CH2:41][C@H:40]2[CH3:45])[N:35]([CH2:3][C:4]([N:6]2[C:14]3[C:9](=[N:10][CH:11]=[C:12]([CH2:15][C:16]4[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=4)[CH:13]=3)[C:8]([CH3:24])([CH3:23])[CH2:7]2)=[O:5])[CH2:34][C@H:33]1[CH3:46])=[O:31])([CH3:28])([CH3:26])[CH3:27]

참가 물질

7

반응물 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 70980298(2R,5S)-tert-butyl 2-methyl-5-(((R)-3-methylmorpholino)methyl)piperazine-1-carboxylateHCID 867240432-Chloro-1-[6-(4-fluoro-benzyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridin-1-yl]-ethanone hydrochloride

생성물 1

HCID 70980911(2R,5S)-4-{2-[6-(4-Fluoro-benzyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridin-1-yl]-2-oxo-ethyl}-2-methyl-5-((R)-3-methyl-morpholin-4-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester수율 103.2%

시약·촉매·용매 2

HCID 962Water용매HCID 6342Acetonitrile용매

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온도
20 °C

실험 절차

A mixture of 2-chloro-1-[6-(4-fluoro-benzyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridin-1-yl]-ethanone hydrochloride (6.63 g, 17.96 mmol), (2R,5S)-2-methyl-5-((R)-3-methyl-morpholin-4-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester (5.62 g, 17.96 mmol), potassium carbonate (9.95 g, 72 mmol) and finely ground potassium iodide (5.98 g, 36 mmol) in acetonitrile (40 mL) was stirred at 20° C. for 1 h. Water (200 mL) was added and mixture stirred for 0.2 h, then the mixture was extracted with EtOAc (200 mL). The organic phase was dried (Na2SO4) and evaporated in vacuo to give the title compound (11.3 g) as an oil, used without further purification. 1H NMR (Me-d3-OD): 8.28-8.19 (1H, m), 8.13-8.04 (1H, m), 7.25 (2H, dd), 7.04 (2H, t), 4.23-4.13 (1H, m), 4.13-4.04 (2H, m), 4.04-3.95 (3H, m), 3.81-3.58 (4H, m), 3.54 (1H, d), 3.25 (2H, dd), 3.01-2.66 (4H, m), 2.62-2.42 (2H, m), 2.42-2.17 (2H, m), 1.47 (9H, s), 1.43-1.37 (6H, m), 1.29-1.21 (3H, m), 1.01 (3H, d). MS: [M+H]+=610. IR: vC═O 1685, 1653 cm−1.

후처리

  1. stirringmixture stirred for 0.2 h
  2. extractionthe mixture was extracted with EtOAc (200 mL)
  3. dry with materialThe organic phase was dried (Na2SO4)
  4. customevaporated in vacuo

출처 및 근거

ORD 기록
ord-72b89d958b8d41faabd5f723063801ea
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09018214B2

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