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 1482990노트

반응식

HRID 1482990 반응식
[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

참가 물질

5

반응물 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

생성물 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)ethanol수율 56.7%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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온도
-78 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-31831af20d2942418bb318d3dd92fe4a
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09416135B2

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