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 1482987ノート

反応式

HRID 1482987 の反応式
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

参加物

5

反応物 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

生成物 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-ol収率 68.7%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

反応条件

温度
-10 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-374b23191a1141619dee3449e876bce0
出典データセット
uspto-grants-2016_08
特許番号
US09416135B2

反応ノート

読み込み中…