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

HRID 1521537ノート

反応式

HRID 1521537 の反応式
[CH:1]1([C:4]2[C:9]([C:10](OC)=[O:11])=[CH:8][N:7]=[C:6]([N:14]3[CH2:19][CH2:18][N:17]4[C:20]5[CH:26]=[C:25]([S:27]([CH3:30])(=[O:29])=[O:28])[C:24]([C:31](OC)=[O:32])=[CH:23][C:21]=5[N:22]=[C:16]4[C@H:15]3[CH:35]([CH3:37])[CH3:36])[N:5]=2)[CH2:3][CH2:2]1.CC(C[AlH]CC(C)C)C.[NH4+].[Cl-]>C(Cl)Cl.C1(C)C=CC=CC=1>[CH:1]1([C:4]2[C:9]([CH2:10][OH:11])=[CH:8][N:7]=[C:6]([N:14]3[CH2:19][CH2:18][N:17]4[C:20]5[CH:26]=[C:25]([S:27]([CH3:30])(=[O:29])=[O:28])[C:24]([CH2:31][OH:32])=[CH:23][C:21]=5[N:22]=[C:16]4[C@H:15]3[CH:35]([CH3:37])[CH3:36])[N:5]=2)[CH2:2][CH2:3]1.[CH:1]1([C:4]2[C:9]([CH2:10][OH:11])=[CH:8][N:7]=[C:6]([N:14]3[CH2:19][CH2:18][N:17]4[C:20]5[CH:26]=[C:25]([S:27]([CH3:30])(=[O:29])=[O:28])[C:24]([CH2:31][OH:32])=[CH:23][C:21]=5[N:22]=[C:16]4[C@@H:15]3[CH:35]([CH3:37])[CH3:36])[N:5]=2)[CH2:2][CH2:3]1

参加物

7

反応物 3

HCID 14487Diisobutylaluminum hydrideHCID 25517Ammonium ChlorideHCID 89816093(R)-methyl 2-(4-cyclopropyl-5-(methoxycarbonyl)pyrimidin-2-yl)-1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate

生成物 2

HCID 71736793(R)-(4-cyclopropyl-2-(8-(hydroxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)pyrimidin-5-yl)methanol収率 24.5%HCID 71736794(S)-(4-cyclopropyl-2-(8-(hydroxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)pyrimidin-5-yl)methanol収率 15.1%

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
-78 °C

実験手順

To a solution of (R)-methyl 2-(4-cyclopropyl-5-(methoxycarbonyl)pyrimidin-2-yl)-1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate (50 mg, 0.1 mmol) in CH2Cl2 (2 mL) was added DIBAL H (1M in toluene, 1 mL, 1 mmol) at −78° C. The mixture was stirred at −78° C. for 1 h and then rt for 1 h. Sat. NH4Cl solution (5 mL) was added slowly at 0° C. and the mixture was filtered. The aqueous layer was extracted with EtOAc (3×5 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The residue was purified by preparative TLC and then SFC separation to afford (R)-(4-cyclopropyl-2-(8-(hydroxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)pyrimidin-5-yl)methanol (11.50 mg, 24.5% yield, isomer 1) as a colorless oil and (S)-(4-cyclopropyl-2-(8-(hydroxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)pyrimidin-5-yl)methanol (7.10 mg, 15.1% yield, isomer 2) as a colorless oil.

後処理

  1. waitrt for 1 h
  2. filtrationthe mixture was filtered
  3. extractionThe aqueous layer was extracted with EtOAc (3×5 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified by preparative TLC
  9. customSFC separation

出典と根拠

ORDレコード
ord-2b3295412d4143f29c4eaf28cab1255e
出典データセット
uspto-grants-2015_07
特許番号
US09073931B2

反応ノート

読み込み中…