N-methyl-2-pyrrolidone → HCID 67112014、化合物

HRID 2088903ノート

反応式

HRID 2088903 の反応式
Cl[C:2]1[C:3]2[CH:11]([CH3:12])[CH2:10][C:9](=[O:13])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.Cl.Cl.Cl.[N:17]1([CH2:22][CH2:23][N:24]2[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[N:26]=[C:25]2[CH:33]2[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]2)[CH2:21][CH2:20][CH2:19][CH2:18]1.CN1CCCC1=O.C(N(C(C)C)CC)(C)C>O>[CH3:12][CH:11]1[C:3]2[C:2]([N:36]3[CH2:35][CH2:34][CH:33]([C:25]4[N:24]([CH2:23][CH2:22][N:17]5[CH2:18][CH2:19][CH2:20][CH2:21]5)[CH:28]=[C:27]([C:29]([F:31])([F:32])[F:30])[N:26]=4)[CH2:38][CH2:37]3)=[N:7][CH:6]=[N:5][C:4]=2[NH:8][C:9](=[O:13])[CH2:10]1

参加物

6

反応物 4

HCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 866665664-chloro-5-methyl-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-oneHCID 866665764-(1-(2-(pyrrolidin-1-yl)ethyl)-4-(trifluoromethyl)-1H-imidazol-2-yl)piperidine trihydrochloride

生成物 1

HCID 67112014HCID 67112014、化合物

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
200 °C

実験手順

Add 4-chloro-5-methyl-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one (0.22 g, 1.11 mmol), 4-(1-(2-(pyrrolidin-1-yl)ethyl)-4-(trifluoromethyl)-1H-imidazol-2-yl)piperidine trihydrochloride (0.57 g, 1.2 eq), N-methylpyrrolidinone (10 mL) and diisopropylethylamine (1.16 mL, 6.0 eq) in a microwave tube. Seal the tube and heat in a microwave reactor at 200° C. for 30 minutes. Dilute the reaction mixture with water and extract with ethyl acetate. Wash with saturated aqueous sodium chloride. Dry the organics over anhydrous sodium sulfate, filter, and concentrate in vacuo. Purify by normal phase chromatography, eluting with a 1-10% methanol/dichloromethane gradient, to give 5-methyl-4-(4-(1-(2-(pyrrolidin-1-yl)ethyl)-4-(trifluoromethyl)-1H-imidazol-2-yl)piperidin-1-yl)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one as a racemate (0.19 g, 36%). MS (ES) m/z=478 [M]+. Chiral separation (Chiralpak AD-H, 30% ethanol/70% CO2 w/0.2% isopropylamine) provides enantiomer 1 (>99% ee) and (R)-5-methyl-4-(4-(1-(2-(pyrrolidin-1-yl)ethyl)-4-(trifluoromethyl)-1H-imidazol-2-yl)piperidin-1-yl)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one as enantiomer 2 (>99% ee). MS (ES) m/z=478 [M]+ for both compounds.

後処理

  1. customSeal the tube
  2. extractionextract with ethyl acetate
  3. washWash with saturated aqueous sodium chloride
  4. dry with materialDry the organics over anhydrous sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customPurify by normal phase chromatography
  8. washeluting with a 1-10% methanol/dichloromethane gradient

出典と根拠

ORDレコード
ord-4eac708f0aa34b63b7b0e9bf95028647
出典データセット
uspto-grants-2013_05
特許番号
US08436002B2

反応ノート

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