Diisobutylaluminum hydride → 1-(2-(8-(hydroxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)-4-(trifluoromethyl)pyrimidin-5-yl)ethanol

HRID 1482990ノート

反応式

HRID 1482990 の反応式
[C:1]([C:4]1[C:5]([C:34]([F:37])([F:36])[F:35])=[N:6][C:7]([N:10]2[CH2:15][CH2:14][N:13]3[C:16]4[CH:22]=[C:21]([S:23]([CH3:26])(=[O:25])=[O:24])[C:20]([C:27](OC)=[O:28])=[CH:19][C:17]=4[N:18]=[C:12]3[C@H:11]2[CH:31]([CH3:33])[CH3:32])=[N:8][CH:9]=1)(=[O:3])[CH3:2].CC(C[AlH]CC(C)C)C.[NH4+].[Cl-]>C(Cl)Cl>[OH:28][CH2:27][C:20]1[C:21]([S:23]([CH3:26])(=[O:24])=[O:25])=[CH:22][C:16]2[N:13]3[CH2:14][CH2:15][N:10]([C:7]4[N:6]=[C:5]([C:34]([F:37])([F:36])[F:35])[C:4]([CH:1]([OH:3])[CH3:2])=[CH:9][N:8]=4)[CH:11]([CH:31]([CH3:32])[CH3:33])[C:12]3=[N:18][C:17]=2[CH:19]=1

参加物

5

反応物 3

HCID 14487Diisobutylaluminum hydrideHCID 25517Ammonium ChlorideHCID 89815953(R)-methyl 2-(5-acetyl-4-(trifluoromethyl)pyrimidin-2-yl)-1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate

生成物 1

HCID 781644011-(2-(8-(hydroxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)-4-(trifluoromethyl)pyrimidin-5-yl)ethanol収率 56.7%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
-78 °C

実験手順

To a 50 mL three-necked flask containing (R)-methyl 2-(5-acetyl-4-(trifluoromethyl)pyrimidin-2-yl)-1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate (150 mg, 0.278 mmol) in DCM (3 mL) was added DIBAL-H (1.10 mL, 1.11 mmol, 1.0 M in toluene) dropwise at −78° C. under N2. The mixture was stirred at −78° C. for 3 h. Sat. NH4Cl solution (10 mL) was added at −78° C. and the mixture was filtered. The aqueous layer was extracted with DCM (3×20 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by preparative TLC to give the racemic mixture (81.0 mg, 56.7% yield) as a white solid. The racemic mixture was purified by SFC separation to give isomer 1 (10.60 mg, 47.1% yield) as a white solid, isomer 2 (7.10 mg, 31.6% yield) as a white solid, isomer 3 (4.70 mg, 26.1% yield) as a white solid and isomer 4 (6.00 mg, 33.3% yield) as a white solid.

後処理

  1. filtrationthe mixture was filtered
  2. extractionThe aqueous layer was extracted with DCM (3×20 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by preparative TLC

出典と根拠

ORDレコード
ord-31831af20d2942418bb318d3dd92fe4a
出典データセット
uspto-grants-2016_08
特許番号
US09416135B2

反応ノート

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