Cyclopentylamine → N-Cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-8-amine

HRID 456693

반응식

HRID 456693 반응식
Cl[C:2]1[C:3]2[N:4]([C:8]([C:18]3[CH:23]=[CH:22][N:21]=[C:20]([NH:24][CH:25]4[CH2:29][CH2:28][CH2:27][CH2:26]4)[N:19]=3)=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[N:10]=2)[CH:5]=[CH:6][CH:7]=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:88]1([NH2:93])[CH2:92][CH2:91][CH2:90][CH2:89]1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH:88]1([NH:93][C:2]2[C:3]3[N:4]([C:8]([C:18]4[CH:23]=[CH:22][N:21]=[C:20]([NH:24][CH:25]5[CH2:29][CH2:28][CH2:27][CH2:26]5)[N:19]=4)=[C:9]([C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=4)[N:10]=3)[CH:5]=[CH:6][CH:7]=2)[CH2:92][CH2:91][CH2:90][CH2:89]1

참가 물질

8

반응물 5

HCID 2906CyclopentylamineHCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 102014694-[8-Chloro-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl]-N-cyclopentylpyrimidin-2-amine

생성물 1

HCID 10161456N-Cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-8-amine수율 55%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 962Water용매

반응 조건

온도
100 °C

실험 절차

To a solution of 4-[8-chloro-2-(4-fluorophenyl)imidazo[1,2-α]pyridin-3-yl]-N-cyclopentyl-2-pyrimidinamine (200 mg, 0.49 mmol) in cyclopentylamine (10 mL) was added, successively, racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (91 mg, 0.15 mmol), cesium carbonate (0.24 g, 0.7 mmol) and palladium(II) acetate (22 mg, 0.1 mmol). The resulting mixture was heated in a sealed tube at 100° C. for 18 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. The phases were separated and the organic layer was washed with water and brine. The combined organics were dried (magnesium sulfate), filtered and concentrated to a solid. This solid was purified by silica gel chromatography (1:1 hexanes:ethyl acetate) to give N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(4-fluorophenyl)imidazo[1,2-α]pyridin-8-amine (120 mg, 55%) as a solid. 1H NMR (CDCl3) δ 8.80 (d, 1H), 8.06 (d, 1H), 7.62 (q, 2H), 7.10 (t, 2H), 6.76 (t, 1H), 6.34 (d, 1H), 6.27 (d, 1H), 5.22 (d, 2H), 4.34 (m, 1H), 3.93 (m, 1H), 2.0–2.1 (m, 4H), 1.4–1.9 (m, 12H); 19F NMR (CDCl3) δ −113.9; MS m/z 457 (M+1).

후처리

  1. temperatureThe solution was cooled to room temperature
  2. customThe phases were separated
  3. washthe organic layer was washed with water and brine
  4. dry with materialThe combined organics were dried (magnesium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated to a solid
  7. customThis solid was purified by silica gel chromatography (1:1 hexanes:ethyl acetate)

출처 및 근거

ORD 기록
ord-f800a20d6bfc415b8df42aaa962eac75
출처 데이터셋
uspto-grants-2007_03
특허 번호
US07186714B2

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