Acetonitrile → N-[6-(2-hydroxy-1-phenyl-ethylamino)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide

HRID 2069302ノート

反応式

HRID 2069302 の反応式
[CH2:1]1[O:9][CH:2]1[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(#N)C.[NH2:13][C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][C:23]=1[C:24]([F:27])([F:26])[F:25])[NH:20][C:19](=[O:28])[N:18]([NH:29][S:30]([CH3:33])(=[O:32])=[O:31])[C:17]2=[O:34]>>[OH:9][CH2:1][CH:2]([NH:13][C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][C:23]=1[C:24]([F:26])([F:25])[F:27])[NH:20][C:19](=[O:28])[N:18]([NH:29][S:30]([CH3:33])(=[O:32])=[O:31])[C:17]2=[O:34])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

参加物

4

反応物 3

HCID 6342AcetonitrileHCID 7276Styrene Oxide2 回HCID 11964604N-(6-amino-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulfonamide

生成物 1

HCID 69343558N-[6-(2-hydroxy-1-phenyl-ethylamino)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide収率 18%

実験手順

To a solution of 0.101 ml (0.887 mmol) of styrene oxide in 1 ml acetonitril 242 mg (1.77 mmol) zinc chloride are added and the mixture is stirred for 15 minutes. To the resulting white suspension 50 mg (0.148 mmol) of N-(6-amino-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulfonamide are added and the mixture is stirred at 70° C. for 90 minutes. Another 0.017 ml (0.147 mmol) of styrene oxide are added and the mixture is stirred for another 30 minutes at 70° C. The solvent is evaporated by rotavapor evaporation. The residue is dissolved in ethyl acetate and washed with an aqueous solution of potassium carbonate (1M) and with an aqueous solution of citric acid (10%). The crude product is purified by reversed phase (C18) chromatography using an acetonitril-water gradient. Upon lyophilisation 12 mg (18%) of N-[6-(2-hydroxy-1 -phenyl-ethylamino)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide are obtained as a yellowish solid. MS (ES+): m/e =459 (M+H+).

後処理

  1. stirringthe mixture is stirred at 70° C. for 90 minutes
  2. stirringthe mixture is stirred for another 30 minutes at 70° C
  3. customThe solvent is evaporated by rotavapor evaporation
  4. dissolutionThe residue is dissolved in ethyl acetate
  5. washwashed with an aqueous solution of potassium carbonate (1M) and with an aqueous solution of citric acid (10%)
  6. customThe crude product is purified by reversed phase (C18) chromatography

出典と根拠

ORDレコード
ord-f81a067dd81942528a36e5447aaf4cd0
出典データセット
uspto-grants-2012_10
特許番号
US08299085B2

反応ノート

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