Cyclopentylamine → N-cyclopentyl-2-(4-fluorophenyl)-3-[2-(1-pyrrolid inyl)-4-pyrimidinyl]-6-(trifluoromethyl)pyrazolo[1,5-alpha]pyridin-7-amine

HRID 1796533ノート

反応式

HRID 1796533 の反応式
Cl[C:2]1[N:7]2[N:8]=[C:9]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[C:10]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]([N:17]4[CH2:21][CH2:20][CH2:19][CH2:18]4)[N:12]=3)=[C:6]2[CH:5]=[CH:4][C:3]=1[C:29]([F:32])([F:31])[F:30].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH:85]1([NH2:90])[CH2:89][CH2:88][CH2:87][CH2:86]1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCOCC>[CH:85]1([NH:90][C:2]2[N:7]3[N:8]=[C:9]([C:22]4[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=4)[C:10]([C:11]4[CH:16]=[CH:15][N:14]=[C:13]([N:17]5[CH2:21][CH2:20][CH2:19][CH2:18]5)[N:12]=4)=[C:6]3[CH:5]=[CH:4][C:3]=2[C:29]([F:32])([F:31])[F:30])[CH2:89][CH2:88][CH2:87][CH2:86]1

参加物

8

反応物 4

HCID 2906CyclopentylamineHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 221809127-Chloro-2-(4-fluorophenyl)-3-[2-(1-pyrrolidinyl)-4-pyrimidinyl]-6-(trifluoromethyl)pyrazolo[1,5-a]pyridine

生成物 1

HCID 10142258N-cyclopentyl-2-(4-fluorophenyl)-3-[2-(1-pyrrolid inyl)-4-pyrimidinyl]-6-(trifluoromethyl)pyrazolo[1,5-alpha]pyridin-7-amine収率 63%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 1140Toluene溶媒HCID 3283Diethyl Ether溶媒

実験手順

To a solution of 7-chloro-2-(4-fluorophenyl)-3-[2-(1-pyrrolidinyl)-4-pyrimidinyl]-6-(trifluoromethyl)pyrazolo[1,5-a]pyridine (54 mg, 0.12 mmol) in toluene (3 mL) was added successively racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (9.2 mg, 0.013 mmol), cesium carbonate (57 mg, 0.17 mmol), cyclopentylamine (0.5 mL, 5.0 mmol), and palladium (II) acetate (2 mg, 0.009 mmol). The resultant mixture was heated at 85° C. for 6 hours at which time the reaction was judged complete by thin layer chromatography. The solution was cooled to room temperature and ether was added. The organic layer was washed with water and brine. The aqueous layer was extracted with ether and the combined organics dried over magnesium sulfate. Filtration and concentration followed by flash chromatography (12:1 to 8:1 hexanes-ethyl acetate) provided N-cyclopentyl-2-(4-fluorophenyl)-3-[2-(1-pyrrolidinyl)-4-pyrimidinyl]-6-(trifluoromethyl)pyrazolo[1,5-a]pyridin-7-amine (37 mg, 63%) as an oil. 1H NMR (CDCl3): δ 8.16 (d, 1 H), 7.84 (d, 1 H), 7.68 (dd, 2 H), 7.49 (d, 1 H), 7.18 (t, 2 H), 6.55 (d, 1 H), 6.29 (d, 1 H), 4.57 (m, 1 H), 3.68 (m, 4 H), 2.13–2.05 (m, 6 H), 1.84–1.65 (m, 6 H); 19F NMR (CDCl3) δ −55.33, −112.78; MS m/z 511 (M+1). This material was taken up in ether and treated with hydrochloric acid in ether to yield a bright yellow powder which was isolated by filtration as a hydrochloride salt.

後処理

  1. washThe organic layer was washed with water and brine
  2. extractionThe aqueous layer was extracted with ether
  3. dry with materialthe combined organics dried over magnesium sulfate
  4. filtrationFiltration and concentration

出典と根拠

ORDレコード
ord-6c7405c6f6ec4c898302653cdb2c78e0
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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