Dimethyl Sulfoxide → HCID 178511605, 화합물

HRID 1623421노트

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HRID 1623421 반응식
[Cl:1][C:2]1[C:3]([C:16]2[C:21]([Cl:22])=[CH:20][N:19]=[C:18](F)[CH:17]=2)=[N:4][C:5]([NH:8][CH2:9][CH:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[CH:6][CH:7]=1.CS(C)=O.[C@H:28]1([NH2:35])[CH2:33][CH2:32][C@H:31]([NH2:34])[CH2:30][CH2:29]1>C(OCC)(=O)C>[NH2:34][C@H:31]1[CH2:32][CH2:33][C@H:28]([NH:35][C:18]2[CH:17]=[C:16]([C:3]3[C:2]([Cl:1])=[CH:7][CH:6]=[C:5]([NH:8][CH2:9][CH:10]4[CH2:15][CH2:14][O:13][CH2:12][CH2:11]4)[N:4]=3)[C:21]([Cl:22])=[CH:20][N:19]=2)[CH2:29][CH2:30]1

참가 물질

5

반응물 3

HCID 679Dimethyl SulfoxideHCID 581271593,5'-dichloro-2'-fluoro-N-((tetrahydro-2H-pyran-4-yl)methyl)-2,4'-bipyridin-6-amine2회HCID 178511674HCID 178511674, 화합물

생성물 1

HCID 178511605HCID 178511605, 화합물수율 101.2%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

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온도
100 °C

실험 절차

To 3,5′-dichloro-2′-fluoro-N-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridin-6-amine (Intermediate G) (250 mg, 0.702 mmol) was added DMSO (3 ml) and trans-cyclohexane-1,4-diamine (952 mg, 6.32 mmol). The reaction mixture was stirred at 100° C. for 20 hours and the reaction progress was followed by LCMS. The reaction mixture was cooled, diluted with 250 ml ethyl acetate, washed with saturated sodium bicarbonate (1×), water (3×) and concentrated to constant mass, giving 320 mg of product as a free base, which was used without further purification. A portion of the title compound, 25 mg was purified by prep LC and lyapholized to give 17.6 mg of the title compound as a TFA salt. LCMS (m/z): 450.2 (MH+), retention time=0.58 min.; 1H NMR (300 MHz, METHANOL-d4, 25° C.) δ ppm 1.16-1.76 (m, 8H) 1.76-1.98 (m, 1H) 2.04-2.27 (m, 4H) 3.06-3.16 (m, 1H) 3.19 (d, J=6.74 Hz, 2H) 3.37 (t, J=11.87 Hz, 2H) 3.62-3.77 (m, 1H) 3.92 (dd, J=11.28, 3.08 Hz, 2H) 6.61 (d, J=8.79 Hz, 1H) 6.73 (s, 1H) 7.50 (d, J=9.08 Hz, 1H) 8.04 (s, 1H).

후처리

  1. temperatureThe reaction mixture was cooled
  2. washwashed with saturated sodium bicarbonate (1×), water (3×)
  3. concentrationconcentrated to constant mass

출처 및 근거

ORD 기록
ord-90f2148f347343c08c51965555591056
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08778951B2

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