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 1475521ノート

反応式

HRID 1475521 の反応式
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]

参加物

7

反応物 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

生成物 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 ester収率 103.2%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
20 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-72b89d958b8d41faabd5f723063801ea
出典データセット
uspto-grants-2015_04
特許番号
US09018214B2

反応ノート

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