Hydrochloric Acid → n-[6-(1-Methoxy-ethyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2h-quinazolin-3-yl]-methanesulfonamide

HRID 1894013ノート

反応式

HRID 1894013 の反応式
CO[C:3](=[O:19])[C:4]1[CH:9]=[C:8]([CH:10]([O:12][CH3:13])[CH3:11])[C:7]([C:14]([F:17])([F:16])[F:15])=[CH:6][C:5]=1[NH2:18].CC[N:22]([CH2:25]C)CC.[CH3:27][S:28]([NH:31]N)(=[O:30])=[O:29].[OH-:33].[Na+].Cl>C1COCC1.CCOC(C)=O.CCCCC>[CH3:13][O:12][CH:10]([C:8]1[CH:9]=[C:4]2[C:5](=[CH:6][C:7]=1[C:14]([F:15])([F:16])[F:17])[NH:18][C:25](=[O:33])[N:22]([NH:31][S:28]([CH3:27])(=[O:30])=[O:29])[C:3]2=[O:19])[CH3:11]

参加物

9

反応物 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 269268MethanesulfonohydrazideHCID 119652962-Amino-5-(1-methoxy-ethyl)-4-trifluoromethyl-benzoic acid methyl ester

生成物 1

HCID 11965297n-[6-(1-Methoxy-ethyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2h-quinazolin-3-yl]-methanesulfonamide収率 78.3%

試薬・触媒・溶媒 3

HCID 8003Pentane溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒2 回

実験手順

A solution of 2-amino-5-(1-methoxy-ethyl)-4-trifluoromethyl-benzoic acid methyl ester (190 mg, 0.69 mmol) in THF was treated with (CCl3O)2CO (178 mg, 0.6 mmol) and the mixture was stirred at r.t. for 15 min under argon. To this solution was added Et3N (84 μL, 0.6 mmol) and the mixture was stirred for another 3 h at r.t. The mixture was then treated with CH3SO2NHNH2 (66 mg, 0.6 mmol) and stirred for 1 h at r.t. Aqueous sodium hydroxide (1M, 3 mL, 3 mmol) was subsequently added and the solution was stirred for 18 h at r.t. The mixture was acidified with aqueous hydrochloric acid (4N) until pH=3-4, and then diluted with EtOAc. The layers were separated and the organic phase was then washed once with water, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (silica gel 60, hexanes/EtOAc 2:1) to give a pale yellow solid, which was dissolved in EtOAc. Pentane was then added until a white product precipitated. This mixture was allowed to stand at 0° C. for 16 h, and the white solid was then filtered and dried in vacuo at 60° C. to provide N-[6-(1-methoxy-ethyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide (180 mg, 0.47 mmol, 68%) as a white powder, m.p. 233-236° C., ESI-MS: m/z 382 [M+H]+.

後処理

  1. stirringthe mixture was stirred for another 3 h at r.t
  2. stirringstirred for 1 h at r.t
  3. stirringthe solution was stirred for 18 h at r.t
  4. customThe layers were separated
  5. washthe organic phase was then washed once with water
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by column chromatography (silica gel 60, hexanes/EtOAc 2:1)
  10. customto give a pale yellow solid, which
  11. customprecipitated
  12. waitto stand at 0° C. for 16 h
  13. filtrationthe white solid was then filtered
  14. customdried in vacuo at 60° C.

出典と根拠

ORDレコード
ord-6c42893cb5824b0a9b929fd8d8fe6c47
出典データセット
uspto-grants-2013_08
特許番号
US08513268B2

反応ノート

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