Methoxyacetic Acid → HCID 57794565、化合物

HRID 2099373ノート

反応式

HRID 2099373 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:47][C@H:48]4[CH2:53][CH2:52][CH2:51][NH:50][CH2:49]4)=[C:42]([O:45][CH3:46])[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.[CH3:64][O:65][CH2:66][C:67](O)=[O:68]>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:47][C@H:48]4[CH2:53][CH2:52][CH2:51][N:50]([C:67](=[O:68])[CH2:66][O:65][CH3:64])[CH2:49]4)=[C:42]([O:45][CH3:46])[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 12251Methoxyacetic AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68908613HCID 68908613、化合物

生成物 1

HCID 57794565HCID 57794565、化合物収率 80.9%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

HATU (0.24 g) was added to a solution of N-(3-chloro-2-fluorophenyl)-6-methoxy-7-[(3S)-piperidin-3-yloxy]quinazolin-4-amine dihydrochloride (250 mg), diisopropylethylamine (0.37 ml) and methoxyacetic acid (0.054 g) in methylene chloride (9 ml) and the mixture was stirred at room temperature for 2.5 hours. Methylene chloride (20 ml) was added and the organic layer was washed with aqueous sodium hydroxide (2M, 30 ml) and water (30 ml). The resulting product was purified by flash column chromatography eluting with methanol (3%) and methylene chloride (97%) gave a foam. This was re-precipitated by stirring in diethyl ether (20 ml) to give the title product as a white solid (0.202 g); 1H NMR Spectrum: (DMSO d6 373K) 1.60 (m, 1H), 1.88 (m, 2H), 2.10 (m, 1H), 3.32 (s, 3H), 3.51 (m, 2H), 3.62 (m, 1H), 3.87 (m, 1H), 3.98 (s, 3H), 4.02 (d, J=14 Hz, 1H), 4.12 (d, J=14 Hz, 1H), 4.66 (m, 1H), 7.26 (m, 1H), 7.33 (s, 1H), 7.43 (m, 1H), 7.62 (m, 1H), 7.83 (s, 1H), 8.40 (s, 1H), 9.34 (br s, 1H); Mass Spectrum: (M+H)+ 475.

後処理

  1. washthe organic layer was washed with aqueous sodium hydroxide (2M, 30 ml) and water (30 ml)
  2. customThe resulting product was purified by flash column chromatography
  3. washeluting with methanol (3%) and methylene chloride (97%)
  4. customgave a foam
  5. customThis was re-precipitated
  6. stirringby stirring in diethyl ether (20 ml)

出典と根拠

ORDレコード
ord-dac002e72e7046bbae25709f96481338
出典データセット
uspto-grants-2009_08
特許番号
US07569577B2

反応ノート

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