4-Chloro-6,7-dimethoxyquinazoline → 3-[4-(6,7-Dimethoxy-quinazolin-4-ylamino)-2-methyl-phenoxy]-benzoic acid hydrochloride

HRID 731904ノート

反応式

HRID 731904 の反応式
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.C([O:20][C:21](=[O:37])[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([O:28][C:29]2[CH:34]=[CH:33][C:32]([NH2:35])=[CH:31][C:30]=2[CH3:36])[CH:23]=1)(C)(C)C>ClCCCl.C(O)(C)(C)C>[ClH:1].[CH3:13][O:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][C:8]=1[O:14][CH3:15])[N:5]=[CH:4][N:3]=[C:2]2[NH:35][C:32]1[CH:33]=[CH:34][C:29]([O:28][C:24]2[CH:23]=[C:22]([CH:27]=[CH:26][CH:25]=2)[C:21]([OH:37])=[O:20])=[C:30]([CH3:36])[CH:31]=1

参加物

5

反応物 2

HCID 27693644-Chloro-6,7-dimethoxyquinazolineHCID 53439210tert-Butyl 3-(4-amino-2-methylphenoxy)benzoate

生成物 1

HCID 690525853-[4-(6,7-Dimethoxy-quinazolin-4-ylamino)-2-methyl-phenoxy]-benzoic acid hydrochloride収率 93%

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒HCID 6386tert-Butanol溶媒

反応条件

温度
90 °C

実験手順

To a suspension of 4-chloro-6,7-dimethoxy-quinazoline (3.0 g, 13.35 mmol) in 1,2-dichloroethane (40 mL) and tert-butyl alcohol (40 mL) was added 3-(4-amino-2-methyl-phenoxy)-benzoic acid tert-butyl ester (3.99 g, 13.35 mmol). The reaction was heated at 90° C. for 90 minutes. The reaction was then cooled to room temperature and hydrogen chloride gas was bubbled through the solution for 40 minutes. A small amount of hot methanol was added to solublize the gummed solids. Solids then crashed out upon cooling. The solids were filtered and rinsed with cold ethyl acetate. The solids were further dried at 50° C. in a vacuum oven, yielding light yellow solids as the mono hydrochloride salt (5.79 g, 93%). 1H NMR (400 MHz, DMSO-d6) δ 11.39(bs, 1H), 8.82(s, 1H), 8.29(s, 1H), 7.64(d, J=7.06 Hz, 1H), 7.63(s, 1H), 7.55(d, J=8.72 Hz, 1H), 7.50(t, J=15.78, 7.89 Hz, 1H), 7.33(s, 1H), 7.30(s, 1H), 7.08(d, J=8.72 Hz, 1H), 3.98(s, 3H), 3.96(s, 3H), 2.17(s, 3H), LRMS (M+): 732.3, (M−): 430.3.

後処理

  1. temperatureThe reaction was then cooled to room temperature
  2. customhydrogen chloride gas was bubbled through the solution for 40 minutes
  3. additionA small amount of hot methanol was added
  4. temperatureupon cooling
  5. filtrationThe solids were filtered
  6. washrinsed with cold ethyl acetate
  7. customThe solids were further dried at 50° C. in a vacuum oven

出典と根拠

ORDレコード
ord-77a331c5857d4f179228c6d02a69affc
出典データセット
uspto-grants-2009_09
特許番号
US07585869B2

反応ノート

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