Sodium hydride → tert-Butyl 3-{3-[(cyclopentyl{4-[(4-oxoquinazolin-3(4H)-yl)methyl]phenyl}acetyl)amino]-2-methylphenyl}propanoate

HRID 877254Notes

Reaction equation

HRID 877254 reaction equation
[H-].[Na+].[N:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6](=[O:13])[NH:5][CH:4]=1.Br[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([CH:22]([CH:42]2[CH2:46][CH2:45][CH2:44][CH2:43]2)[C:23]([NH:25][C:26]2[C:27]([CH3:41])=[C:28]([CH2:32][CH2:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH:29]=[CH:30][CH:31]=2)=[O:24])=[CH:18][CH:17]=1.[Cl-].[NH4+]>CN(C=O)C.C1CCCCC1.C(OCC)(=O)C>[CH:42]1([CH:22]([C:19]2[CH:20]=[CH:21][C:16]([CH2:15][N:5]3[C:6](=[O:13])[C:7]4[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=4)[N:3]=[CH:4]3)=[CH:17][CH:18]=2)[C:23]([NH:25][C:26]2[C:27]([CH3:41])=[C:28]([CH2:32][CH2:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH:29]=[CH:30][CH:31]=2)=[O:24])[CH2:43][CH2:44][CH2:45][CH2:46]1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 58136306Tert-butyl 3-[3-({[4-(bromomethyl)phenyl](cyclopentyl)acetyl}amino)-2-methylphenyl]propanoateHCID 1354087534(1H)-Quinazolinone

Product 1

HCID 58136737tert-Butyl 3-{3-[(cyclopentyl{4-[(4-oxoquinazolin-3(4H)-yl)methyl]phenyl}acetyl)amino]-2-methylphenyl}propanoate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 21867204Cyclohexane ethylacetateSolvent

Conditions

Temperature
0 °C

Procedure

15 mg (0.39 mmol, content 60%) of sodium hydride were added to a solution of 34 mg (0.23 mmol) of quinazolin-4(3H)-one in 5 ml of DMF, and the mixture was stirred under an atmosphere of argon at 0° C. for 30 min. 100 mg (0.19 mmol) of tert-butyl 3-[3-({[4-(bromomethyl)phenyl](cyclopentyl)acetyl}amino)-2-methylphenyl]propanoate, dissolved in 1 ml of DMF, were then added to the reaction solution, and the latter was slowly warmed to toom temperature. After the reaction had gone to completion (monitored by TLC; cyclohexane/ethyl acetate 2:1), 1 ml of saturated ammonium chloride solution was added and the reaction mixture was purified directly by preparative HPLC. This gave 28 mg (0.05 mmol, 25% of theory) of the racemic title compound.

Workup

  1. additionwere then added to the reaction solution
  2. temperaturethe latter was slowly warmed
  3. additionwas added
  4. customthe reaction mixture was purified directly by preparative HPLC

Sources & evidence

ORD record
ord-08ba5439bd8e4846910e8f0a0334ecc6
Source dataset
uspto-grants-2015_03
Patent number
US08987256B2

Reaction notes

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