Dimethyl Carbonate → HCID 178517394, compound

HRID 277842Notes

Reaction equation

HRID 277842 reaction equation
[CH:1]1([Mg]Br)[CH2:3][CH2:2]1.[Mg].C1(Br)CC1.[NH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[CH:19]=2)=[CH:14][C:13]=1[C:25]#[N:26].[C:27](=O)(OC)[O:28]C.[Cl-].[NH4+]>C1COCC1.C(OCC)(=O)C>[Cl:24][C:20]1[CH:19]=[C:18]([C:15]2[CH:14]=[C:13]3[C:12](=[CH:17][CH:16]=2)[NH:11][C:27](=[O:28])[N:26]=[C:25]3[CH:1]2[CH2:3][CH2:2]2)[CH:23]=[CH:22][CH:21]=1

Participants

9

Reactant 6

HCID 12021Dimethyl CarbonateHCID 25517Ammonium ChlorideHCID 78037BromocyclopropaneHCID 5462224MagnesiumHCID 97945754-Amino-3'-chloro-biphenyl-3-carbonitrileHCID 178418630HCID 178418630, compound

Product 1

HCID 178517394HCID 178517394, compoundYield 18%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

Prepared using a similar procedure as described in the literature (Tucker et al. J. Med. Chem., 1994, 37, 2437-2444). To a solution of cyclopropylmagnesium bromide prepared from magnesium (0.9 g, 37 mmol) and cyclopropyl bromide (3.2 mL, 40 mmol) in anhydrous THF was added at 50° C. under nitrogen a solution of 4-amino-3′-chloro-biphenyl-3-carbonitrile (2.3 g, 10 mmol) in anhydrous THF. After addition, the reaction mixture was kept at 50° C. for 30 minutes under nitrogen and treated with dimethyl carbonate in a dropwise manner. The reaction solution was stirred at 50° C. under nitrogen for 30 minutes and cooled to ambient temperature. A saturated aqueous ammonium chloride solution (30 mL) was added followed by addition of ethyl acetate (80 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (3×40 mL). The combined organic layers were washed with brine and dried with MgSO4. After removal of the solvent, the residue was purified by a flash chromatography (silica gel, methylene chloride:methanol/25:1) to give 6-(3-chlorophenyl)-4-cyclopropyl-1H-quinazolin-2-one as a yellowish solid (0.55 g, 18%): mp 189-190° C.; 1H-NMR (DMSO-d6) δ 11.71 (s, 1H, D2O exchangeable), 8.56 (d, 1H, J=1.3 Hz), 8.09 (dd, 1H, J=8.6, 1.6 Hz), 7.92 (s, 1H), 7.77 (d, 1H, J=7.7 Hz), 7.52 (t, 1H, J=7.9 Hz), 7.45 (d, 1H, J=8.1 Hz), 7.36 (d, 1H, J=8.6 Hz), 3.15 (m, 1H), 1.20 (m, 4H); MS (CI) m/z 297 ([M+H]+, 100%); Anal. Calc. For C17H13ClN2O: C, 69.98, H, 4.49, N, 9.23. Found: C, 67.98, H, 4.46, N, 9.10.

Workup

  1. customPrepared
  2. additionAfter addition
  3. temperaturecooled to ambient temperature
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with ethyl acetate (3×40 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried with MgSO4
  8. customAfter removal of the solvent
  9. customthe residue was purified by a flash chromatography (silica gel, methylene chloride:methanol/25:1)

Sources & evidence

ORD record
ord-8d1e18cf86a2419e996f497a0a50852f
Source dataset
uspto-grants-2002_03
Patent number
US06358948B1

Reaction notes

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