Morpholine → N-{3-[4-(3-Methyl-4-phenoxy-phenylamino)-quinazolin-6-yl]-prop-2-ynyl}-2-morpholin-4-yl-acetamide

HRID 1264065ノート

反応式

HRID 1264065 の反応式
Cl[CH2:2][C:3]([NH:5][CH2:6][C:7]#[C:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[N:15]=[CH:14][N:13]=[C:12]2[NH:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[C:22]([CH3:33])[CH:21]=1)=[O:4].[NH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1>C1(C)C=CC=CC=1>[CH3:33][C:22]1[CH:21]=[C:20]([NH:19][C:12]2[C:11]3[C:16](=[CH:17][CH:18]=[C:9]([C:8]#[C:7][CH2:6][NH:5][C:3](=[O:4])[CH2:2][N:34]4[CH2:39][CH2:38][O:37][CH2:36][CH2:35]4)[CH:10]=3)[N:15]=[CH:14][N:13]=2)[CH:25]=[CH:24][C:23]=1[O:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

参加物

4

反応物 2

HCID 8083MorpholineHCID 541744332-Chloro-N-{3-[4-(3-methyl4-phenoxy-phenylamino)-quinazolin-6-yl]-prop-2-ynyl}-acetamide

生成物 1

HCID 18616457N-{3-[4-(3-Methyl-4-phenoxy-phenylamino)-quinazolin-6-yl]-prop-2-ynyl}-2-morpholin-4-yl-acetamide

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

実験手順

To a solution of 2-Chloro-N-{3-[4-(3-methyl-4-phenoxy-phenylamino)-quinazolin-6-yl]-prop-2-ynyl}-acetamide (63 mg; 0.12 mmol) in toluene (10 ml) was added 3 equivalents of morpholine (31 mg) and the mixture heated at reflux overnight. The reaction was cooled to room temperature and the morpholine salts were filtered out and the solvent removed from the filtrate. The residue was redissolved in CH2Cl2 with a small amount of methanol and HCl gas was bubbled through the solution for 2-3 minutes. The solution was then concentrated to 2-3 ml, diluted with ethyl acetate and filtered to obtain N-{3-[4-(3-Methyl-4-phenoxy-phenylamino)-quinazolin-6-yl]-prop-2-ynyl}-2-morpholin-4-yl-acetamide as a yellow/brown solid (65 mg; 94%). 1H NMR (400 MHz; CD3OD) δ 2.27 (3H, s), 3.21 (2H, m), 3.56 (2H, m), 3.87 (2H, m), 4.04 (2H, m), 4.09 (2H, s), 4.36 (2H, s), 6.93 (3H, d, J=8.4), 7.09 (1H, t, J=7.4 Hz), 7.34 (2H, t, J=8 Hz), 7.54 (1H, dd), 7.65 (1 H, s), 7.82 (1H, d, J=8.8 Hz), 8.06 (1H, d, J=8.4 Hz), 8.76 (1H, s), 8.80 (1H, s). Irms(M+): 508.0; (M−): 506.0.

後処理

  1. temperaturethe mixture heated
  2. temperatureat reflux overnight
  3. filtrationthe morpholine salts were filtered out
  4. customthe solvent removed from the filtrate
  5. dissolutionThe residue was redissolved in CH2Cl2 with a small amount of methanol and HCl gas
  6. customwas bubbled through the solution for 2-3 minutes
  7. concentrationThe solution was then concentrated to 2-3 ml
  8. additiondiluted with ethyl acetate
  9. filtrationfiltered

出典と根拠

ORDレコード
ord-8e561bb4453f416d83acb05f0f988623
出典データセット
uspto-grants-2003_04
特許番号
US06541481B2

反応ノート

読み込み中…