Cyclopentylamine → N-[3-(2-anilino-4-pyrimidinyl)-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-yl]-N-cyclopentylamine

HRID 8510

반응식

HRID 8510 반응식
Cl[C:2]1[CH:7]=[CH:6][N:5]2[N:8]=[C:9]([C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=3)[C:10]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]([NH:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[N:12]=3)=[C:4]2[CH:3]=1.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+].C(OCC)(=O)C.[CH:89]1([NH2:94])[CH2:93][CH2:92][CH2:91][CH2:90]1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[NH:17]([C:13]1[N:12]=[C:11]([C:10]2[C:9]([C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=3)=[N:8][N:5]3[CH:6]=[CH:7][C:2]([NH:94][CH:89]4[CH2:93][CH2:92][CH2:91][CH2:90]4)=[CH:3][C:4]=23)[CH:16]=[CH:15][N:14]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

참가 물질

8

반응물 5

HCID 2906CyclopentylamineHCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-2회HCID 112470274-[5-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-phenyl-2-pyrimidinamine

생성물 1

HCID 22350049N-[3-(2-anilino-4-pyrimidinyl)-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-yl]-N-cyclopentylamine수율 36%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매2회HCID 962Water용매

반응 조건

온도
100 °C

실험 절차

To a solution of 4-[5-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-phenyl-2-pyrimidinamine (100 mg, 0.24 mmol) in cyclopentylamine (5 mL) was added successively racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (72 mg), cesium carbonate (200 mg), and palladium (II) acetate (16 mg). The resulting mixture was stirred at 100° C. for 24 hours, then additional racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (72 mg) and palladium (II) acetate (16 mg) were added and the reaction stirred at 100° C. for additional 24 hours, at which time the reaction was judged complete by thin layer chromatography. The solution was cooled to room temperature and ethyl acetate and water were added to the reaction mixture. The phases were separated, and the aqueous phase again extracted with ethyl acetate. The combined organic phases were dried (magnesium sulfate), filtered and concentrated. The resulting residue was purified by flash chromatography (1:1 hexanes:ethyl acetate) to give N-[3-(2-anilino-4-pyrimidinyl)-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridin-5-yl]-N-cyclopentylamine (40 mg, 36%) as a solid. 1H NMR (CDCl3): δ 8.21 (d, 1H), 8.13 (d, 1H), 7.65 (m, 4H), 7.4–7.24 (m, 4H), 7.18 (t, 21H), 7.06 (t, 1H), 6.44 (d 1H), 6.30 (dd, 1H), 4.16 (d, 1H), 3.68 (m, 1H), 1.4–2.2 (m, 8H); 19F-NMR (CDCl3): δ−113.32; MS m/z 466 (M+1).

후처리

  1. stirringthe reaction stirred at 100° C. for additional 24 hours, at which time the reaction
  2. temperatureThe solution was cooled to room temperature
  3. customThe phases were separated
  4. extractionthe aqueous phase again extracted with ethyl acetate
  5. dry with materialThe combined organic phases were dried (magnesium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was purified by flash chromatography (1:1 hexanes:ethyl acetate)

출처 및 근거

ORD 기록
ord-87058de6158440a7af624a3373595eef
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07087618B2

연결된 노트

불러오는 중…