Sodium hydride → (2S,3S,5R)-2-Benzyl-3-[(5-bromo-pyrimidin-2-yl)-(3-chloro-5-trifluoromethyl-benzyl)-amino]-5-ethyl-pyrrolidine-1-carboxylic acid isopropyl ester

HRID 409428ノート

反応式

HRID 409428 の反応式
[CH:1]([O:4][C:5]([N:7]1[C@H:11]([CH2:12][CH3:13])[CH2:10][C@H:9]([NH:14][C:15]2[N:20]=[CH:19][C:18]([Br:21])=[CH:17][N:16]=2)[C@@H:8]1[CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:6])([CH3:3])[CH3:2].[H-].[Na+].[Cl:31][C:32]1[CH:33]=[C:34]([CH:37]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:39]=1)[CH2:35]Br>CN(C=O)C>[CH:1]([O:4][C:5]([N:7]1[C@H:11]([CH2:12][CH3:13])[CH2:10][C@H:9]([N:14]([C:15]2[N:20]=[CH:19][C:18]([Br:21])=[CH:17][N:16]=2)[CH2:35][C:34]2[CH:37]=[C:38]([C:40]([F:41])([F:42])[F:43])[CH:39]=[C:32]([Cl:31])[CH:33]=2)[C@@H:8]1[CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:6])([CH3:2])[CH3:3]

参加物

5

反応物 3

HCID 24758Sodium hydride2 回HCID 37146721-(Bromomethyl)-3-chloro-5-(trifluoromethyl)benzeneHCID 59614351(2S,3S,5R)-2-benzyl-3-(5-bromo-pyrimidin-2-ylamino)-5-ethyl-pyrrolidine-1-carboxylic acid isopropyl ester

生成物 1

HCID 42633349(2S,3S,5R)-2-Benzyl-3-[(5-bromo-pyrimidin-2-yl)-(3-chloro-5-trifluoromethyl-benzyl)-amino]-5-ethyl-pyrrolidine-1-carboxylic acid isopropyl ester収率 73.2%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a suspension of (2S,3S,5R)-2-benzyl-3-(5-bromo-pyrimidin-2-ylamino)-5-ethyl-pyrrolidine-1-carboxylic acid isopropyl ester (0.064 mmol; 28.6 mg) and sodium hydride (60% dispersion in mineral oil, 0.19 mmol; 7.6 mg) in DMF (0.6 mL) is added 3-chloro-5-trifluoromethylbenzyl bromide (0.13 mmol; 35.6 mg) at room temperature under N2. After 3.5 hours, additional sodium hydride (60% dispersion in mineral oil, 0.19 mmol; 7.6 mg) is added to the suspension. The reaction mixture is stirred for 20 minutes, and quenched with water and saturated aqueous ammonium chloride solution. The product is extracted three times with EtOAc. The combined organic layer is washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue is purified by column chromatography on silica gel (eluent: n-hexane/EtOAc) to give (2S,3S,5R)-2-Benzyl-3-[(5-bromo-pyrimidin-2-yl)-(3-chloro-5-trifluoromethyl-benzyl)-amino]-5-ethyl-pyrrolidine-1-carboxylic acid isopropyl ester (30.0 mg, 73%); ESI-MS m/z: 639 [M+1]+, Retention time 2.68 min (condition A).

後処理

  1. customquenched with water and saturated aqueous ammonium chloride solution
  2. extractionThe product is extracted three times with EtOAc
  3. washThe combined organic layer is washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue is purified by column chromatography on silica gel (eluent: n-hexane/EtOAc)

出典と根拠

ORDレコード
ord-7809089de0224b668716ca9d48bb6531
出典データセット
uspto-grants-2014_06
特許番号
US08759365B2

反応ノート

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