Diethyl Ether → N-cyclopentyl-4-[2-(4-fluorophenyl)-6-(trifluoromethyl)-pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinamine

HRID 1797068ノート

反応式

HRID 1797068 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.Cl.[CH:29]1([NH:34][C:35]([NH2:37])=[NH:36])[CH2:33][CH2:32][CH2:31][CH2:30]1.C(=O)([O-])[O-].[K+].[K+].CCOCC>CN1CCCC1=O.O>[CH:29]1([NH:34][C:35]2[N:37]=[C:5]([C:7]3[C:8]([C:20]4[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=4)=[N:9][N:10]4[CH:15]=[C:14]([C:16]([F:18])([F:17])[F:19])[CH:13]=[CH:12][C:11]=34)[CH:4]=[CH:3][N:36]=2)[CH2:33][CH2:32][CH2:31][CH2:30]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 178479367HCID 178479367、化合物

生成物 1

HCID 22174839N-cyclopentyl-4-[2-(4-fluorophenyl)-6-(trifluoromethyl)-pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinamine収率 56%

試薬・触媒・溶媒 2

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

反応条件

温度
140 °C

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 (314 mg, 0.83 mmol)) in 1-methyl-2-pyrrolidinone (3 mL) was added N-cyclopentylguanidine hydrochloride (271 mg, 1.66 mmol) and potassium carbonate (229 mg, 1.66 mmol). The mixture was heated at 140° C. 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 (4:1 hexanes-ethyl acetate) to give N-cyclopentyl-4-[2-(4-fluorophenyl)-6-(trifluoromethyl)pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinamine (204 mg, 56%) as a white solid. 1 H NMR (CDCl3): δ 8.84 (s, 1 H), 8.51 (d, 1 H), 8.11 (d, 1 H), 7.64 (dd, 2 H), 7.44 (dd, 1 H), 7.17 (t, 2 H), 6.33 (d, 1H), 5.17 (d, 1H), 4.34 (m, 1H), 2.15–2.06 (m, 2 H), 1.84–1.52 (m, 6 H); 19F NMR (CDCl3): δ −62.70, −112.25; MS m/z 442 (M+1); mp 155–156° C.

後処理

  1. temperatureUpon cooling to room temperature
  2. washThe organics were washed with brine
  3. extractionthe aqueous layer was extracted with ether
  4. dry with materialThe combined organics were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography on silica (4:1 hexanes-ethyl acetate)

出典と根拠

ORDレコード
ord-6aff180aee6144338b6520bc928834c2
出典データセット
uspto-grants-2006_04
特許番号
US07034030B2

反応ノート

読み込み中…