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Dimethylformamide → 3-(4,4'-Dimethoxybenzhydryl)-6-(N-methyl-N-isobutyrylcarbamoyl)-amino-2-propyl-quinazolin-4(3H)-one

HRID 1770146
Notes
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Reaction equation

HRID 1770146 reaction equation
[H-].[Na+].N[C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[N:10]=[C:9]([CH2:14][CH2:15][CH3:16])[N:8]([CH:17]([C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=1)[C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1)[C:7]2=[O:34].[CH2:35]([O:39]C(Cl)=O)[CH:36]([CH3:38])[CH3:37].C[Si](C)(C)[N-:45][Si](C)(C)C.[Li+].IC.[CH3:55][N:56]([CH:58]=[O:59])C>C1COCC1.CCOC(C)=O>[CH3:33][O:32][C:29]1[CH:28]=[CH:27][C:26]([CH:17]([N:8]2[C:7](=[O:34])[C:6]3[C:11](=[CH:12][CH:13]=[C:4]([C:58](=[O:59])[N:56]([CH3:55])[C:35](=[O:39])[CH:36]([CH3:37])[CH3:38])[C:5]=3[NH2:45])[N:10]=[C:9]2[CH2:14][CH2:15][CH3:16])[C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)=[CH:31][CH:30]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

9

Reactant 6

HCID 6228Dimethylformamide2×HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 62365Isobutyl chloroformateHCID 2733832Lithium hexamethyldisilazaneHCID 19934842HCID 19934842, compound

Product 1

HCID 67789925
3-(4,4'-Dimethoxybenzhydryl)-6-(N-methyl-N-isobutyrylcarbamoyl)-amino-2-propyl-quinazolin-4(3H)-one
Yield 71%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 81.5 mg (2.7 mmol) of 80% NaH in 3 ml of dry DMF at 0° C. under nitrogen was added dropwise a solution of 1.03 g (2.5 mmol) of 6-amino-3-(4,4'-dimethoxybenzhydryl)-2-propyl-quinazolin-4(3H)-one dissolved in 3 ml of DMF. The resulting mixture was stirred for 30 minutes and was then treated with 0.35 ml (2.7 mmol) of isobutylchloroformate neat. The solution was stirred for 30 minutes and then treated with 2.97 ml (2.97 mmol) of a 1M solution of lithium hexamethyldisilazide in THF. The dark solution was stirred for a further 30 minutes at 0° C. and then was treated with 0.2 ml (3.26 mmol) of iodomethane neat. The mixture was stirred overnight at room temperature, poured into 50 ml of EtOAc and washed consecutively with water (2×10 ml), brine (1×10 ml) and dried over MgSO4 . The product was purified by flash chromatography over silica gel eluting with 30% EtOAc/hexanes to give 0.9 g (1.7 mmol) of an oil. 71% yield. 1H-NMR (CDCl3): 0.82-0.91 (m, 6H), 0.96 (d, 3H, J=6.8 Hz), 1.52 (m, 2H), 1.88 (m, 1H), 2.67 (bt, 2H), 3.35 (s, 3H), 3.80 (s, 6H), 3.90 (d, 2H, J=6.6 Hz), 6.87 (d, 4H, J=8.8 Hz), 7.20 (d, 4H, J=8.8 Hz), 7.61 (m, 1H), 7.78 (m, 1H), 8.01 (d, 1H, 2 Hz).

Workup

  1. stirringThe solution was stirred for 30 minutes
  2. stirringThe dark solution was stirred for a further 30 minutes at 0° C.
  3. stirringThe mixture was stirred overnight at room temperature
  4. washwashed consecutively with water (2×10 ml), brine (1×10 ml)
  5. dry with materialdried over MgSO4
  6. customThe product was purified by flash chromatography over silica gel eluting with 30% EtOAc/hexanes

Sources & evidence

ORD record
ord-353f06e924294ef19b2f9c8a8c555194
Source dataset
uspto-grants-1995_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US05385894

Reaction notes

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