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

HRID 1521511ノート

反応式

HRID 1521511 の反応式
[CH:1]([CH:4]1[N:9]([C:10]2[N:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[C:13]([C:20](OCC)=[O:21])=[CH:12][N:11]=2)[CH2:8][CH2:7][N:6]2[C:25]3[CH:31]=[C:30]([S:32]([CH3:35])(=[O:34])=[O:33])[CH:29]=[CH:28][C:26]=3[N:27]=[C:5]12)([CH3:3])[CH3:2].CC(C[AlH]CC(C)C)C.[NH4+].[Cl-]>C1(C)C=CC=CC=1>[CH:1]([CH:4]1[N:9]([C:10]2[N:15]=[C:14]([C:16]([F:18])([F:19])[F:17])[C:13]([CH2:20][OH:21])=[CH:12][N:11]=2)[CH2:8][CH2:7][N:6]2[C:25]3[CH:31]=[C:30]([S:32]([CH3:35])(=[O:33])=[O:34])[CH:29]=[CH:28][C:26]=3[N:27]=[C:5]12)([CH3:3])[CH3:2]

参加物

5

反応物 3

HCID 14487Diisobutylaluminum hydrideHCID 25517Ammonium ChlorideHCID 71735988ethyl 2-(1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)-4-(trifluoromethyl)pyrimidine-5-carboxylate

生成物 1

HCID 71735989(2-(1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)-4-(trifluoromethyl)pyrimidin-5-yl)methanol収率 63%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
-78 °C

実験手順

To a solution of ethyl 2-(1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)-4-(trifluoromethyl)pyrimidine-5-carboxylate (10 mg, 0.02 mmol, prepared according to example 3) in anhydrous toluene (0.5 mL) was added DIBAL-H (0.2 mL, 0.20 mmol, 1M in THF) dropwise at −78° C. under N2. The mixture was stirred at −78° C. for 2 h. Sat. NH4Cl (5 mL) at −78° C. was added to the mixture, which was then extracted with EtOAc (3×5 mL). The combined organic layers were washed with brine (5 mL), dried over anhydrous Na2SO4, filtered, concentrated and then purified by basic preparative HPLC to afford a racemic mixture of (2-(1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)-4-(trifluoromethyl)pyrimidin-5-yl)methanol (5.80 mg, 63% yield) as a white solid. LC-MS m/z 470.1 [M+H]+. 1H NMR (CDCl3 400 MHz): δ 8.68 (s, 1H), 8.01 (s, 1H), 7.93-7.81 (m, 2H), 6.11 (d, J=8.0 Hz, 1H), 5.38 (dd, J=5.2 Hz, J=14.4 Hz, 1H), 4.74 (s, 2H), 4.38-4.30 (m, 1H), 4.25-4.15 (m, 1H), 3.86-3.76 (m, 1H), 3.10 (s, 3H), 2.56-2.47 (m, 1H), 1.32 (d, J=6.8 Hz, 3H), 1.08 (d, J=6.8 Hz, 3H).

後処理

  1. extractionwas then extracted with EtOAc (3×5 mL)
  2. washThe combined organic layers were washed with brine (5 mL)
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by basic preparative HPLC
  7. customto afford

出典と根拠

ORDレコード
ord-001f10960e6d4821a6a2afba5ae11c7d
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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