Sodium hydride → HCID 25060729, compound

HRID 2244055Notes

Reaction equation

[H-].[Na+].[CH3:3][C:4]1[C:12]2[C:11](=[O:13])[CH2:10][C:9]([CH3:15])([CH3:14])[CH2:8][C:7]=2[NH:6][CH:5]=1.F[C:17]1[C:26]([F:27])=[C:25]2[C:20]([C:21]([NH2:28])=[N:22][CH:23]=[N:24]2)=[CH:19][CH:18]=1>CN(C=O)C>[NH2:28][C:21]1[C:20]2[C:25](=[C:26]([F:27])[C:17]([N:6]3[C:7]4[CH2:8][C:9]([CH3:15])([CH3:14])[CH2:10][C:11](=[O:13])[C:12]=4[C:4]([CH3:3])=[CH:5]3)=[CH:18][CH:19]=2)[N:24]=[CH:23][N:22]=1

Participants

Conditions

Temperature: 50 °C

Procedure

Sodium hydride (60% suspension in mineral oil, 50 mg, 1.3 mmol) is added to a solution of 3,6,6-Trimethyl-1,5,6,7-tetrahydro-indol-4-one (50 mg, 0.29 mmol) in anhydrous DMF (1 mL). This mixture is stirred at room temperature for 5 minutes before 7,8-Difluoro-quinazolin-4-ylamine (75 mg, 0.41 mmol) is added. After 10 minutes at room temperature, the reaction mixture is heated at 50° C. overnight. The cooled reaction mixture is partitioned between ethyl acetate and water to remove DMF, and the organic layer is concentrated to dryness via Rotovap. The resulting crude residue is further purified through two consecutive silica gel columns (0%-8% of methanol in DCM, gradient) to afford 1-(4-Amino-8-fluoro-quinazolin-7-yl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-indol-4-one (15 mg, not optimized) as white solid. LC/MS m/z=339 [M+H]+.

Workup

additionis added
customThe cooled reaction mixture
customis partitioned between ethyl acetate and water
customto remove DMF
concentrationthe organic layer is concentrated to dryness via Rotovap
customThe resulting crude residue is further purified through two consecutive silica gel columns (0%-8% of methanol in DCM, gradient)

Sources & evidence

ORD record: ord-e1d71b929efb43378e9777baf1feb46b
Source dataset: uspto-grants-2010_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07678803B2

Reaction notes

Loading…