Diisopropylethylamine → N-(3-chloro-2-fluorophenyl)-6-{[1-(isoxazol-5-ylcarbonyl)piperidin-4-yl]oxy}-7-methoxyquinazolin-4-amine

HRID 1175061ノート

反応式

HRID 1175061 の反応式
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.Cl.[Cl:27][C:28]1[C:29]([F:54])=[C:30]([NH:34][C:35]2[C:44]3[C:39](=[CH:40][C:41]([O:52][CH3:53])=[C:42]([O:45][CH:46]4[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]4)[CH:43]=3)[N:38]=[CH:37][N:36]=2)[CH:31]=[CH:32][CH:33]=1.C(N(C(C)C)CC)(C)C.[O:64]1[C:68]([C:69](O)=[O:70])=[CH:67][CH:66]=[N:65]1>C(Cl)Cl>[Cl:27][C:28]1[C:29]([F:54])=[C:30]([NH:34][C:35]2[C:44]3[C:39](=[CH:40][C:41]([O:52][CH3:53])=[C:42]([O:45][CH:46]4[CH2:47][CH2:48][N:49]([C:69]([C:68]5[O:64][N:65]=[CH:66][CH:67]=5)=[O:70])[CH2:50][CH2:51]4)[CH:43]=3)[N:38]=[CH:37][N:36]=2)[CH:31]=[CH:32][CH:33]=1

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 20605991,2-Oxazole-5-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 574768654-(3-Chloro-2-fluoroanilino)-7-methoxy-6-(piperidin-4-yloxy)quinazoline dihydrochloride

生成物 1

HCID 11443377N-(3-chloro-2-fluorophenyl)-6-{[1-(isoxazol-5-ylcarbonyl)piperidin-4-yl]oxy}-7-methoxyquinazolin-4-amine収率 35%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

HATU (0.31 g) was added to a solution of N-(3-chloro-2-fluorophenyl)-7-methoxy-6-(piperidin-4-yloxy)quinazolin-4-amine dihydrochloride (300 mg), diisopropylethylamine (0.45 ml) and isoxazole-5-carboxylic acid (0.1 g) in methylene chloride (9 ml). The resulting mixture was stirred at room temperature for 2.5 hrs. Methylene chloride (20 ml) was added and the organics washed with aqueous sodium hydroxide (2M, 30 ml) and water (30 ml). The crudes were then purified by flash column chromatography eluting with methanol/methylene chloride (2.5/97.5). Fractions containing the desired product were evaporated to a white foam which was triturated with diethyl ether (20 ml) to give N-(3-chloro-2-fluorophenyl)-6-{[1-(isoxazol-5-ylcarbonyl)piperidin-4-yl]oxy}-7-methoxyquinazolin-4-amine as a white solid (0.110 g). 1H NMR Spectrum: (DMSO d6 373K) 1.88 (m, 2H), 2.09 (m, 2H), 3.61 (m, 2H), 3.84 (m, 2H), 3.96 (s, 3H), 4.78 (m, 1H), 6.87 (s, 1H), 7.29 (m, 1H), 7.29 (s, 1H), 7.42 (m, 1H), 7.59 (m, 1H), 7.93 (s, 1H), 8.39 (s, 1H), 8.64 (s, 1H), 9.28 (br s, 1H); Mass Spectrum: (M+H)+ 498.

後処理

  1. washthe organics washed with aqueous sodium hydroxide (2M, 30 ml) and water (30 ml)
  2. customThe crudes were then purified by flash column chromatography
  3. washeluting with methanol/methylene chloride (2.5/97.5)
  4. additionFractions containing the desired product
  5. customwere evaporated to a white foam which
  6. customwas triturated with diethyl ether (20 ml)

出典と根拠

ORDレコード
ord-18208f2f723f4d2e8c08234be7a10121
出典データセット
uspto-grants-2010_11
特許番号
US07838530B2

反応ノート

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