Methoxyacetyl chloride → 4-(2-Fluoro-5-methoxycarbonyloxy-4-methylanilino)-6-methoxy-7-methoxyacetamidoquinazoline

HRID 634745ノート

反応式

HRID 634745 の反応式
[CH3:1][O:2][CH2:3][C:4](Cl)=[O:5].Cl.[NH2:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([NH:19][C:20]3[CH:25]=[C:24]([O:26][C:27]([O:29][CH3:30])=[O:28])[C:23]([CH3:31])=[CH:22][C:21]=3[F:32])=[N:14][CH:15]=[N:16]2)=[CH:11][C:10]=1[O:33][CH3:34]>C(Cl)Cl.N1C=CC=CC=1>[F:32][C:21]1[CH:22]=[C:23]([CH3:31])[C:24]([O:26][C:27]([O:29][CH3:30])=[O:28])=[CH:25][C:20]=1[NH:19][C:13]1[C:12]2[C:17](=[CH:18][C:9]([NH:8][C:4](=[O:5])[CH2:3][O:2][CH3:1])=[C:10]([O:33][CH3:34])[CH:11]=2)[N:16]=[CH:15][N:14]=1

参加物

5

反応物 2

HCID 96623Methoxyacetyl chloride2 回HCID 212603307-Amino4-(2-fluoro-5-methoxycarbonyloxy-4-methylanilino)-6-methoxyquinazoline hydrochloride

生成物 1

HCID 107894254-(2-Fluoro-5-methoxycarbonyloxy-4-methylanilino)-6-methoxy-7-methoxyacetamidoquinazoline収率 75%

試薬・触媒・溶媒 2

HCID 1049Pyridine溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

Methoxyacetyl chloride (62 μl, 0.68 mmol) was added dropwise to a solution of 7-amino-4-(2-fluoro-5-methoxycarbonyloxy-4-methylanilino)-6-methoxyquinazoline hydrochloride (215 mg, 0.52 mmol) in methylene chloride (5 ml) and pyridine (l.5 ml) at 0° C. and the mixture stirred for 2 hours at 0° C. Further methoxyacetyl chloride (14 μl, 0.15 mmol) was added and the mixture stirred for 20 minutes at 0° C. The reaction mixture was partitioned between ethyl acetate and water and the aqueous layer adjusted to pH9 with saturated aqueous sodium hydrogen carbonate solution. The organic layer was separated, washed with brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/acetonitrile/methanol (60138/2) to give 4-(2-fluoro-5-methoxycarbonyloxy-4-methylanilino)-6-methoxy-7-methoxyacetamidoquinazoline (1 75 mg, 75%) as a white solid.

後処理

  1. stirringthe mixture stirred for 20 minutes at 0° C
  2. customThe reaction mixture was partitioned between ethyl acetate and water
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried (MgSO4)
  6. customthe solvent removed by evaporation
  7. customThe residue was purified by column chromatography
  8. washeluting with methylene chloride/acetonitrile/methanol (60138/2)

出典と根拠

ORDレコード
ord-d0457106ece4412fbf353f3ad134ba07
出典データセット
uspto-grants-2001_02
特許番号
US06184225B2

反応ノート

読み込み中…