Diethyl Ether → 2-(4-Fluorophenyl)-3-[2-(1-pyrrolidinyl)-4-pyrimidinyl]-6-(trifluoromethyl)pyrazolo[1,5-a]pyridine

HRID 1796531ノート

反応式

HRID 1796531 の反応式
CN(C)/[CH:3]=[CH:4]/[C:5]([C:7]1[C:8]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)=[N:9][N:10]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][C:11]=12)=O.S(O)(O)(=O)=O.[N:33]1([C:38](=[NH:40])[NH2:39])[CH2:37][CH2:36][CH2:35][CH2:34]1.C(=O)([O-])[O-].[K+].[K+].CCOCC>CN1CCCC1=O.O>[F:26][C:23]1[CH:22]=[CH:21][C:20]([C:8]2[C:7]([C:5]3[CH:4]=[CH:3][N:39]=[C:38]([N:33]4[CH2:37][CH2:36][CH2:35][CH2:34]4)[N:40]=3)=[C:11]3[CH:12]=[CH:13][C:14]([C:16]([F:17])([F:19])[F:18])=[CH:15][N:10]3[N:9]=2)=[CH:25][CH:24]=1

参加物

7

反応物 4

HCID 3283Diethyl EtherHCID 11430Potassium CarbonateHCID 11501715(2E)-3-(dimethylamino)-1-[2-(4-fluorophenyl)-6-(trifluoromethyl)-pyrazolo[1,5-a]pyridin-3-yl]-2-propen-1-oneHCID 13221242Pyrrolidine-1-carboximidamide, sulfuric acid

生成物 1

HCID 221809222-(4-Fluorophenyl)-3-[2-(1-pyrrolidinyl)-4-pyrimidinyl]-6-(trifluoromethyl)pyrazolo[1,5-a]pyridine収率 71%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

実験手順

To a solution of (2E)-3-(dimethylamino)-1-[2-(4-fluorophenyl)-6-(trifluoromethyl)-pyrazolo[1,5-a]pyridin-3-yl]-2-propen-1-one (100 mg, 0.27 mmol) in 1-methyl-2-pyrrolidinone (3 mL) was added 1-pyrrolidinecarboximidamide sulfate (111 mg, 0.53 mmol), and potassium carbonate (73 mg, 0.53 mmol). The mixture was heated at reflux for 8 hours. Upon cooling to room temperature, ether was added followed by water. The organics were washed with brine, and the aqueous layer was extracted with ether. The combined organics were dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica (6:1 hexanes-ethyl acetate) to give 2-(4-fluorophenyl)-3-[2-(1-pyrrolidinyl)-4-pyrimidinyl]-6-(trifluoromethyl)pyrazolo[1,5-a]pyridine (80 mg, 71%) as a foam. 1H NMR (CDCl3): δ 8.86 (s, 1 H), 8.61 (d, 1 H), 8.19 (m, 1 H), 7.67 (m, 2 H), 7.46 (d, 1 H), 7.19 (m, 2 H), 6.31 (m, 1 H), 3.70 (m, 4 H), 2.08 (m, 4 H); 19F NMR (CDCl3) δ −62.68, −112.27.

後処理

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 8 hours
  3. washThe organics were washed with brine
  4. extractionthe aqueous layer was extracted with ether
  5. dry with materialThe combined organics were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography on silica (6:1 hexanes-ethyl acetate)

出典と根拠

ORDレコード
ord-08585f9499914b67a5794df0c481ed58
出典データセット
uspto-grants-2006_04
特許番号
US07030134B2

反応ノート

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