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Ammonia → (5R)-5-[5-[{2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoyl}(methyl)amino]-4-(4-fluoro-2-methylphenyl)-2-pyridinyl]-2-methyl-D-prolinamide

HRID 69544
ノート
印刷プレビュー

反応式

HRID 69544 の反応式
[F:1][C:2]([F:45])([F:44])[C:3]1[CH:4]=[C:5]([C:13]([CH3:43])([CH3:42])[C:14]([N:16]([CH3:41])[C:17]2[C:18]([C:33]3[CH:38]=[CH:37][C:36]([F:39])=[CH:35][C:34]=3[CH3:40])=[CH:19][C:20]([C@@H:23]3[NH:27][C@@:26]([CH3:32])([C:28](OC)=[O:29])[CH2:25][CH2:24]3)=[N:21][CH:22]=2)=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.CO.[NH3:48]>>[F:11][C:9]([F:12])([F:10])[C:7]1[CH:6]=[C:5]([C:13]([CH3:43])([CH3:42])[C:14]([N:16]([CH3:41])[C:17]2[C:18]([C:33]3[CH:38]=[CH:37][C:36]([F:39])=[CH:35][C:34]=3[CH3:40])=[CH:19][C:20]([C@@H:23]3[NH:27][C@@:26]([CH3:32])([C:28]([NH2:48])=[O:29])[CH2:25][CH2:24]3)=[N:21][CH:22]=2)=[O:15])[CH:4]=[C:3]([C:2]([F:44])([F:45])[F:1])[CH:8]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

4

反応物 3

HCID 222AmmoniaHCID 887MethanolHCID 57965570methyl (5R)-5-[5-[{2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoyl}(methyl)amino]-4-(4-fluoro-2-methylphenyl)-2-pyridinyl]-2-methyl-D-prolinate2 回

生成物 1

HCID 44472503(5R)-5-[5-[{2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoyl}(methyl)amino]-4-(4-fluoro-2-methylphenyl)-2-pyridinyl]-2-methyl-D-prolinamide収率 65.5%

反応条件

温度
60 °C

実験手順

Methyl (5R)-5-[5-[{2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoyl}(methyl)amino]-4-(4-fluoro-2-methylphenyl)-2-pyridinyl]-2-methyl-D-prolinate (Intermediate 9, 25 mg, 0.039 mmol) was dissolved in 7N ammonia solution in MeOH (3 ml, 21.0 mmol) and the reaction mixture was stirred for 48 hours at 60° C. The solvent was evaporated and the residue was purified by flash chromatography on silica gel (Companion system; eluent:from 99:1 Dichloromethane/MeOH to 95:5 Dichloromethane/MeOH; 12 g cartridge) affording the title compound (16 mg, 0.026 mmol, 65.5% yield) as a white solid.

後処理

  1. customThe solvent was evaporated
  2. customthe residue was purified by flash chromatography on silica gel (Companion system; eluent:from 99:1 Dichloromethane/MeOH to 95:5 Dichloromethane/MeOH; 12 g cartridge)

出典と根拠

ORDレコード
ord-3060d9459c9d415aba4a41c48a6d25c6
出典データセット
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08822504B2

反応ノート

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