Methanol → 2-(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)propan-2-ol

HRID 1521520노트

반응식

HRID 1521520 반응식
C[O:2][C:3]([C:5]1[C:6]([S:35]([CH3:38])(=[O:37])=[O:36])=[CH:7][C:8]2[N:12]3[CH2:13][CH2:14][N:15]([C:20]4[N:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[C:23]([C:30]([OH:33])([CH3:32])[CH3:31])=[CH:22][N:21]=4)[C@H:16]([CH:17]([CH3:19])[CH3:18])[C:11]3=[N:10][C:9]=2[CH:34]=1)=O.CC(C[AlH]CC(C)C)C.CO>C(Cl)Cl>[OH:2][CH2:3][C:5]1[C:6]([S:35]([CH3:38])(=[O:36])=[O:37])=[CH:7][C:8]2[N:12]3[CH2:13][CH2:14][N:15]([C:20]4[N:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[C:23]([C:30]([OH:33])([CH3:32])[CH3:31])=[CH:22][N:21]=4)[CH:16]([CH:17]([CH3:19])[CH3:18])[C:11]3=[N:10][C:9]=2[CH:34]=1

참가 물질

5

반응물 3

HCID 887MethanolHCID 14487Diisobutylaluminum hydrideHCID 89816015(R)-methyl-2-(5-(2-hydroxypropan-2-yl)-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 781643372-(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)propan-2-ol수율 68.7%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

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온도
-10 °C

실험 절차

To a solution of (R)-methyl-2-(5-(2-hydroxypropan-2-yl)-4-(trifluoromethyl)pyrimidin-2-yl)-1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate (109 mg, 0.196 mmol) in DCM (4 mL) was added a solution of DIBAL-H in DCM (0.98 mL of a 1.0 M solution, 0.98 mmol) dropwise at −78° C. The reaction slowly warmed to −10° C. over approximately 1 h, at which point 1 mL of MeOH was added to quench the excess DIBAL-H. Sat. aq. Rochelle salt (potassium sodium tartrate (KNaC4H4O6)) solution (5 mL) and DCM (5 mL) were added and the mixture stirred vigorously for 15 min. The DCM layer was separated and the aqueous layer was extracted with DCM (2×5 mL). The DCM layers were combined, dried using Na2SO4 and evaporated to give the crude product. Purification using ISCO FCC eluting with 70% EtOAc in Hexanes gave 71 mg of 2-(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)propan-2-ol as a racemic mixture (69%). LC-MS MS (ESI) m/z 528.25 [M+H]+. 1H NMR (CDCl3, 400 MHz): δ 8.72 (s, 1H), 8.05 (s, 1H), 7.80 (s, 1H), 6.01 (d, J=7.6 Hz, 1H), 5.27 (d, J=4.4 and 14.0 Hz, 1H), 5.00-4.86 (m, 2H), 4.26-4.08 (m, 2H), 3.74-3.67 (m, 1H), 3.15 (s, 3H), 3.15-3.10 (m, 1H), 2.47-2.40 (m, 1H), 1.96 (b, 1H), 1.59 (s, 6H), 1.23 (d, J=6.8 Hz, 3H), 1.10 (d, J=6.8 Hz, 3H).

후처리

  1. customThe reaction
  2. additionwas added
  3. customto quench the excess DIBAL-H
  4. additionSat. aq. Rochelle salt (potassium sodium tartrate (KNaC4H4O6)) solution (5 mL) and DCM (5 mL) were added
  5. customThe DCM layer was separated
  6. extractionthe aqueous layer was extracted with DCM (2×5 mL)
  7. customdried
  8. customevaporated
  9. customto give the crude product
  10. customPurification
  11. washeluting with 70% EtOAc in Hexanes

출처 및 근거

ORD 기록
ord-7f0ef2e4352d4be684d4ee27bc9d51dc
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09073931B2

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