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 1521537노트

반응식

HRID 1521537 반응식
[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

참가 물질

7

반응물 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

생성물 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)methanol수율 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)methanol수율 15.1%

시약·촉매·용매 2

HCID 1140Toluene용매HCID 6344Dichloromethane용매

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온도
-78 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-2b3295412d4143f29c4eaf28cab1255e
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09073931B2

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