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

HRID 2069302Notes

Reaction equation

HRID 2069302 reaction equation
[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

Participants

4

Reactant 3

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

Product 1

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

Procedure

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+).

Workup

  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

Sources & evidence

ORD record
ord-f81a067dd81942528a36e5447aaf4cd0
Source dataset
uspto-grants-2012_10
Patent number
US08299085B2

Reaction notes

Loading…