Methanol → Methyl 4-(2-(4-morpholinophenylamino)-5-methylpyrimidin-4-yl)-2-methoxybenzoate

HRID 449804노트

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HRID 449804 반응식
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[C:10]([O:18][CH3:19])[CH:9]=2)[C:5]([CH3:20])=[CH:4][N:3]=1.[O:21]1[CH2:26][CH2:25][N:24]([C:27]2[CH:33]=[CH:32][C:30]([NH2:31])=[CH:29][CH:28]=2)[CH2:23][CH2:22]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.CO>O1CCOCC1>[O:21]1[CH2:22][CH2:23][N:24]([C:27]2[CH:28]=[CH:29][C:30]([NH:31][C:2]3[N:7]=[C:6]([C:8]4[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[C:10]([O:18][CH3:19])[CH:9]=4)[C:5]([CH3:20])=[CH:4][N:3]=3)=[CH:32][CH:33]=2)[CH2:25][CH2:26]1

참가 물질

6

반응물 4

HCID 887MethanolHCID 75655Benzenamine, 4-(4-morpholinyl)-HCID 521998p-Toluenesulfonic acid monohydrateHCID 86643815Methyl 4-(2-chloro-5-methylpyrimidin-4-yl)-2-methoxybenzoate

생성물 1

HCID 68425754Methyl 4-(2-(4-morpholinophenylamino)-5-methylpyrimidin-4-yl)-2-methoxybenzoate수율 32.8%

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

실험 절차

To a solution of methyl 4-(2-chloro-5-methylpyrimidin-4-yl)-2-methoxybenzoate (165 mg, 0.56 mmol) in 1,4-dioxane (5 mL) was added 4-morpholinoaniline (96 mg, 0.54 mmol) and p-toluenesulfonic acid monohydrate (97 mg, 0.51 mmol). The reaction was heated at reflux for 40 h, cooled to room temperature and partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The aqueous layer was extracted twice more with ethyl acetate and the combined organic fractions were washed twice with 5% aqueous citric acid, water, brine then dried (sodium sulfate) filtered and concentrated to afford the crude product. Trituration with methanol provided methyl 4-(2-(4-morpholinophenylamino)-5-methylpyrimidin-4-yl)-2-methoxybenzoate as a yellow solid (77 mg, 32%); 1H NMR (300 MHz, d6-DMSO) δ 9.36 (s, 1H), 8.38 (s, 1H), 7.76 (d, J=8.1 Hz, 1H), 7.62 (d, J=9.0 Hz, 2H), 7.38 (s, 1H), 7.27 (d, J=8.1 Hz, 1H), 6.88 (d, J=9.0 Hz, 2H), 3.89 (s, 3H), 3.82 (s, 3H), 3.72 (m, 4H), 3.01 (m, 411), 2.12 (s, 3H); LC-ESI-MS (method B): rt 6.7 min.; m/z 435.3 [M+H]+.

후처리

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 40 h
  3. custompartitioned between ethyl acetate and saturated aqueous sodium bicarbonate
  4. extractionThe aqueous layer was extracted twice more with ethyl acetate
  5. washthe combined organic fractions were washed twice with 5% aqueous citric acid, water, brine
  6. dry with materialthen dried (sodium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto afford the crude product

출처 및 근거

ORD 기록
ord-bb42f21bfbd249aab896cf78ecb5bd64
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08486941B2

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