Sodium hydride → 4-(4-Chloroquinazoline-7-ylmethyl)-3-oxopiperazine-1-carboxylic acid tert-butyl ester

HRID 1432924Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][C:10](=[O:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[CH2:16][C:17]1[CH:26]=[C:25]2[C:20]([C:21]([Cl:27])=[N:22][CH:23]=[N:24]2)=[CH:19][CH:18]=1.[H-].[Na+].[NH4+].[Cl-]>C1COCC1.CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:16][C:17]2[CH:26]=[C:25]3[C:20]([C:21]([Cl:27])=[N:22][CH:23]=[N:24]3)=[CH:19][CH:18]=2)[C:10](=[O:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 3-oxopiperazine-1-carboxylic acid tert-butyl ester (3.93 g, 19.6 mmol) and 7-bromomethyl-4-chloroquinazoline, EXAMPLE 7, (5.0 g, 19.6 mmol) in 150 mL of THF and 15 mL of DMF at 0° C. is added a 60% dispersion in mineral oil of NaH (0.79 g, 19.6 mmol). The solution is stirred at 0° C. for 0.5 hours and then is allowed to warm to ambient temperature. After 4 hours, the solution is poured into a saturated solution of NH4Cl. The layers are separated and the organic layer is washed with H2O, and saturated NaCl, dried over MgSO4, filtered and concentrated. The title compound is obtained as a white solid (5.1 g, 13.4 mmol). MS (FAB) m/z 377, 379, (M+H), chlorine pattern.

Workup

temperatureto warm to ambient temperature
waitAfter 4 hours
customThe layers are separated
washthe organic layer is washed with H2O, and saturated NaCl
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-642aa21e054447888435d9fd8919f752
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07612075B2

Reaction notes

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