KOtBu tBuOH → (S)-(4-Fluorophenyl)(4-((5-methyl-1H-pyrazol-3-yl)amino)quinazolin-2-yl)methanol

HRID 929338ノート

反応式

HRID 929338 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[N:19]=[C:18]([NH:20][C:21]3[CH2:25][C:24]([CH3:26])=[N:23][N:22]=3)[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]=2)=[O:9])=[CH:4][CH:3]=1.CC([O-])(C)C.[K+].CC(O)(C)C.[H][H]>CC(O)C.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([C:10]2[N:19]=[C:18]([NH:20][C:21]3[CH:25]=[C:24]([CH3:26])[NH:23][N:22]=3)[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]=2)[OH:9])=[CH:4][CH:3]=1

参加物

5

反応物 3

HCID 23676527KOtBu tBuOHHCID 178418361HCID 178418361、化合物HCID 178434106HCID 178434106、化合物

生成物 1

HCID 56833308(S)-(4-Fluorophenyl)(4-((5-methyl-1H-pyrazol-3-yl)amino)quinazolin-2-yl)methanol収率 82.3%

試薬・触媒・溶媒 1

HCID 21889133Propan-2-ol--water (1/1)溶媒

反応条件

温度
40 °C

実験手順

A stirred mixture of (4-fluorophenyl)(4-(5-methyl-4H-pyrazol-3-ylamino)quinazolin-2-yl)methanone (16.66 g, 48 mmol) and [(R)—P-Phos RuCl2(R)-DAIPEN] (217 mg, 0.192 mmol) at room temperature was subjected to five cycles of pressurizing with nitrogen to 40 psi followed by depressurization. Then 1M KOtBu/tBuOH (576 μL, 0.0.576 mmol) in 9:1 i-PrOH/H2O (4 mL) was added and the mixture was subjected to five cycles of pressurizing with nitrogen to 40 psi followed by depressurization. The stirred mixture was then subjected to ten cycles of pressurizing with hydrogen to 435 psi followed by depressurization. The mixture was then stirred at 900 rpm under hydrogen (435 psi) at 40° C. for 18 hrs. The mixture was allowed to cool to room temperature and then carefully vented. The resulting precipitate was collected by filtration and washed with cold MeOH (100 mL) to afford (S)-(4-fluorophenyl)(4-((5-methyl-1H-pyrazol-3-yl)amino)quinazolin-2-yl)methanol as a white solid (13.8 g). Chiral HPLC indicated a >99% enantiomeric excess of the earlier eluting enantiomer.

後処理

  1. customat room temperature
  2. temperatureto cool to room temperature
  3. filtrationThe resulting precipitate was collected by filtration
  4. washwashed with cold MeOH (100 mL)

出典と根拠

ORDレコード
ord-515ac7bed67a49d985e3f4f2f37522e4
出典データセット
uspto-grants-2016_03
特許番号
US09295672B2

反応ノート

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