2,5-Dimethyl-2H-pyrazole-3-carbonyl chloride → N-{4-[3-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methyl-2-oxopyridin-1(2H)-yl]phenyl}-1,3-dimethyl-1H-pyrazole-5-carboxamide

HRID 632847

반응식

HRID 632847 반응식
[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[CH2:11][N:10]([C:12]3[C:13](=[O:26])[N:14]([C:19]4[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=4)[CH:15]=[CH:16][C:17]=3[CH3:18])[CH2:9][CH2:8][C:6]=2[N:7]=1.[CH3:27][N:28]1[C:32]([C:33](Cl)=[O:34])=[CH:31][C:30]([CH3:36])=[N:29]1>C1COCC1.CCN(CC)CC>[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[CH2:11][N:10]([C:12]3[C:13](=[O:26])[N:14]([C:19]4[CH:20]=[CH:21][C:22]([NH:25][C:33]([C:32]5[N:28]([CH3:27])[N:29]=[C:30]([CH3:36])[CH:31]=5)=[O:34])=[CH:23][CH:24]=4)[CH:15]=[CH:16][C:17]=3[CH3:18])[CH2:9][CH2:8][C:6]=2[N:7]=1

참가 물질

5

반응물 2

HCID 27362992,5-Dimethyl-2H-pyrazole-3-carbonyl chlorideHCID 1212496053-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-1-(4-aminophenyl)-4-methylpyridin-2(1H)-one

생성물 1

HCID 121249566N-{4-[3-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methyl-2-oxopyridin-1(2H)-yl]phenyl}-1,3-dimethyl-1H-pyrazole-5-carboxamide

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8471Triethylamine용매

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온도
40 °C

실험 절차

A solution of 3-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-1-(4-aminophenyl)-4-methylpyridin-2(1H)-one (26 mg, 0.078 mmol) in THF (3 mL) and NEt3 (3 mL) was treated with 1,3-dimethyl-1H-pyrazole-5-carbonyl chloride (16 mg, 0.105 mmol). The reaction was heated to 40° C. and allowed to stir for 5 h. The reaction was cooled and then extracted with EtOAc (3ט10 mL) and water (˜10 mL). The combined organic layers were then washed with ˜20 mL of NaHCO3(aq). The organic layers were then dried over anhydrous Na2SO4, filtered and then concentrated in vacuo. The crude mixture was purified over silica (EtOAc/Hexanes gradient). Following concentration of the appropriate fractions the title compound was collected as a grey solid (25 mg, 76%). 1H NMR (DMSO) δ: 9.52 (s, 1H), 7.92 (s, 1H), 7.81 (d, J=5.6 Hz, 1H), 7.45-7.52 (m, 2H), 7.41 (d, J=6.7 Hz, 1H), 7.24-7.31 (m, 2H), 6.65 (d, J=5.6 Hz, 1H), 6.28 (s, 2H), 6.17 (d, J=7.0 Hz, 1H), 3.96 (br. S, H), 3.29 (s, 2H), 2.66(t, j=5.3 Hz, 2H), 2.35 (s, 3H), 2.18 (s, 3H).

후처리

  1. temperatureThe reaction was cooled
  2. extractionextracted with EtOAc (3ט10 mL) and water (˜10 mL)
  3. washThe combined organic layers were then washed with ˜20 mL of NaHCO3(aq)
  4. dry with materialThe organic layers were then dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude mixture was purified over silica (EtOAc/Hexanes gradient)
  8. customwas collected as a grey solid (25 mg, 76%)

출처 및 근거

ORD 기록
ord-be5e3ef8f27d416d81d8e0a5f310424e
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09321766B1

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