4-Chloro-2-phenylquinazoline → N-(4-{[3-(Dimethylamino)pyrrolidin-1-yl]carbonyl}phenyl)-2-phenylquinazolin-4-amine

HRID 1176059Notes

Reaction equation

[NH2:1][C:2]1[CH:17]=[CH:16][C:5]([C:6]([N:8]2[CH2:12][CH2:11][CH:10]([N:13]([CH3:15])[CH3:14])[CH2:9]2)=[O:7])=[CH:4][CH:3]=1.Cl[C:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[N:22]=[C:21]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[N:20]=1.Cl.N1C=CC=CC=1>C(OC(O)C)C>[CH3:15][N:13]([CH3:14])[CH:10]1[CH2:11][CH2:12][N:8]([C:6]([C:5]2[CH:16]=[CH:17][C:2]([NH:1][C:19]3[C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[N:22]=[C:21]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[N:20]=3)=[CH:3][CH:4]=2)=[O:7])[CH2:9]1

Participants

Conditions

Temperature: 135 °C

Procedure

A mixture of 1-(4-aminobenzoyl)-3-dimethylamino-pyrrolidine (46 mg, 0.2 mmol), 4-chloro-2-phenylquinazoline (48 mg, 0.2 mmol) and pyridine hydrochloride (23 mg, 0.2 mmol) in ethoxyethanol is heated to 135° C. overnight, cooled to room temperature and concentrated in vacuo. The resultant residue is dissolved in a mixture of DMSO, methanol and water and purified by reverse-phase semi-preparative HPLC1 to give the title product as a white powder (15 mg), identified by HPLC and mass spectral analyses. Retention Time, 2.69 min.; MS [438.2 m/e (M+H)]. 1Semi-preparative HPLC Conditions: A=0.02% TFA in water, B=0.02% TFA in acetonitrile, 10-95% B in 8 min., 34 mL/min, 50° C., 215 nm detection, Waters Xterra™ 20×50 mm column.

Workup

temperaturecooled to room temperature
concentrationconcentrated in vacuo
dissolutionThe resultant residue is dissolved in a mixture of DMSO, methanol and water
custompurified by reverse-phase semi-preparative HPLC1

Sources & evidence

ORD record: ord-5a57f2d5d0b44038b6a8f9a36d516b9a
Source dataset: uspto-grants-2010_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07842715B2

Reaction notes

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