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

HRID 1521534ノート

反応式

HRID 1521534 の反応式
[CH:1]([C@H:4]1[N:9]([C:10]2[N:15]=[C:14]([CH3:16])[C:13]([C:17](OC)=[O:18])=[CH:12][N:11]=2)[CH2:8][CH2:7][N:6]2[C:21]3[CH:27]=[C:26]([S:28]([CH3:31])(=[O:30])=[O:29])[C:25]([C:32](OC)=[O:33])=[CH:24][C:22]=3[N:23]=[C:5]12)([CH3:3])[CH3:2].CC(C[AlH]CC(C)C)C.[NH4+].[Cl-]>C1(C)C=CC=CC=1>[OH:33][CH2:32][C:25]1[C:26]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:27][C:21]2[N:6]3[CH2:7][CH2:8][N:9]([C:10]4[N:15]=[C:14]([CH3:16])[C:13]([CH2:17][OH:18])=[CH:12][N:11]=4)[C@H:4]([CH:1]([CH3:2])[CH3:3])[C:5]3=[N:23][C:22]=2[CH:24]=1

参加物

5

反応物 3

HCID 14487Diisobutylaluminum hydrideHCID 25517Ammonium ChlorideHCID 89815891(R)-methyl 1-isopropyl-2-(5-(methoxycarbonyl)-4-methylpyrimidin-2-yl)-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate

生成物 1

HCID 71736792(R)-(2-(8-(hydroxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)-4-methylpyrimidin-5-yl)methanol収率 12.3%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒2 回

反応条件

温度
-78 °C

実験手順

To a solution of (R)-methyl 1-isopropyl-2-(5-(methoxycarbonyl)-4-methylpyrimidin-2-yl)-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate (15 mg, 0.03 mmol) in toluene (2 mL) was added DIBAL H (1M in toluene, 0.3 mL, 0.3 mmol) at −78° C. The mixture was stirred at −78° C. for 2 h and then rt for 30 mins. Sat. NH4Cl solution (5 mL) was added slowly at 0° C. and the mixture was filtered. The aqueous layer was extracted with EtOAc (3×10 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 to afford (R)-(2-(8-(hydroxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)-4-methylpyrimidin-5-yl)methanol (1.6 mg, 12.3% yield) as a colorless oil. LC-MS MS (ESI) m/z 446.2 [M+H]+. 1H NMR (CD3OD 400 MHz): δ 8.26 (s, 1H), 8.23 (s, 1H), 7.99 (s, 1H), 6.00 (d, J=8.8 Hz, 1H), 5.17 (s, 2H), 4.90-4.79 (m, 1H), 4.67 (s, 2H), 4.45-4.44 (m, 1H), 4.25-4.18 (m, 1H), 4.15-4.04 (m, 1H), 3.31 (s, 3H), 2.58-2.49 (m, 1H), 2.45 (s, 3H), 1.25 (d, J=6.8 Hz, 3H), 1.12 (d, J=6.8 Hz, 3H).

後処理

  1. waitrt for 30 mins
  2. filtrationthe mixture was filtered
  3. extractionThe aqueous layer was extracted with EtOAc (3×10 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

出典と根拠

ORDレコード
ord-31194249e9364c9b9c206096fd9904ff
出典データセット
uspto-grants-2015_07
特許番号
US09073931B2

反応ノート

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