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

HRID 589571ノート

反応式

HRID 589571 の反応式
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

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

実験手順

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, 4H), 2.12 (s, 3H); LC-ESI-MS (method B): rt 6.7 min.; m/z 435.3 [M+H]+.

後処理

  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

出典と根拠

ORDレコード
ord-4823677152804d608c3cfcad3f4a5bc1
出典データセット
uspto-grants-2016_01
特許番号
US09233934B2

反応ノート

読み込み中…