Potassium Carbonate → N-(3,4-dichlorophenyl)-7-[({2-[(dimethylamino)methyl]-1,3-thiazol-4-yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine

HRID 2102460ノート

反応式

HRID 2102460 の反応式
Cl.Cl.Cl[CH2:4][C:5]1[N:6]=[C:7]([CH2:10][N:11]([CH3:13])[CH3:12])[S:8][CH:9]=1.[Cl:14][C:15]1[CH:16]=[C:17]([NH:22][C:23]2[C:32]3[C:27](=[CH:28][C:29]([OH:35])=[C:30]([O:33][CH3:34])[CH:31]=3)[N:26]=[CH:25][N:24]=2)[CH:18]=[CH:19][C:20]=1[Cl:21].C(=O)([O-])[O-].[K+].[K+]>>[Cl:14][C:15]1[CH:16]=[C:17]([NH:22][C:23]2[C:32]3[C:27](=[CH:28][C:29]([O:35][CH2:4][C:5]4[N:6]=[C:7]([CH2:10][N:11]([CH3:13])[CH3:12])[S:8][CH:9]=4)=[C:30]([O:33][CH3:34])[CH:31]=3)[N:26]=[CH:25][N:24]=2)[CH:18]=[CH:19][C:20]=1[Cl:21]

参加物

4

反応物 3

HCID 11430Potassium CarbonateHCID 187843234-Chloromethyl-2-dimethylaminomethylthiazole dihydrochloride2 回HCID 1362726214-(3,4-Dichloroanilino)-6-methoxyquinazolin-7(1H)-one

生成物 1

HCID 53630973N-(3,4-dichlorophenyl)-7-[({2-[(dimethylamino)methyl]-1,3-thiazol-4-yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine収率 15%

実験手順

N-{[4-(Chloromethyl)-1,3-thiazol-2-yl]methyl}-N,N-dimethylamine hydrochloride hydrochloride (0.050 g, 0.220 mmol) and 4-[(3,4-dichlorophenyl)amino]-6-(methoxy)quinazolin-7-ol (0.074 g, 0.220 mmol) were suspended in DMP (4 mL) and potassium carbonate (0.152 g, 1.10 mmol) was added. The mixture was stirred at room temperature for 50 h and then at 70° C. for 3.5 h. An additional portion of N-{[4-(chloromethyl)-1,3-thiazol-2-yl]methyl}-N,N-dimethylamine hydrochloride hydrochloride (0.019 g, 0.084 mmol) was added and the mixture was stirred at 70° C. for a further 25 h. The reaction mixture was concentrated in vacuo. and the residue was partitioned between ethyl acetate and brine. The organic portion was washed with 1 N aqueous sodium hydroxide, brine, dried over sodium sulfate, filtered and concentrated in vacuo. to afford a brown solid. Recrystallization from ethyl acetate/diethyl ether afforded the title compound as a pale brown solid (0.016 g, 0.033 mmol, 15% yield). 1H NMR (400 MHz; CDCl3): 2.37 (s, 6H); 3.79 (s, 2H); 4.00 (s, 3H); 5.34 (s, 2H); 7.00 (s, 1H); 7.15 (br s, 1H); 7.34-7.37 (m, 2H); 7.55 (d, 1H); 7.57 (d, 1H); 7.96 (d, 1H); 8.66 (s, 1H); MS (EI) for C22H21Cl2N5O2S: 490 (MH+).

後処理

  1. additionwas added
  2. waitat 70° C. for 3.5 h
  3. stirringthe mixture was stirred at 70° C. for a further 25 h
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. customand the residue was partitioned between ethyl acetate and brine
  6. washThe organic portion was washed with 1 N aqueous sodium hydroxide, brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto afford a brown solid
  11. customRecrystallization from ethyl acetate/diethyl ether

出典と根拠

ORDレコード
ord-557b26f38cfd468a8fc741c4cbd54594
出典データセット
uspto-grants-2009_08
特許番号
US07576074B2

反応ノート

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