Potassium Carbonate → 5-(1-(7-Chloroquinazolin-2-YL)piperidin-4-YL)-7,7-dimethyl-5H-pyrrolo[2,3-B]pyrazin-6(7H)-one

HRID 707396Notes

Reaction equation

Cl.[CH3:2][C:3]1([CH3:19])[C:11]2[C:6](=[N:7][CH:8]=[CH:9][N:10]=2)[N:5]([CH:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)[C:4]1=[O:18].Cl.Cl.CC1(C)C2C(=NC=CC=2)N(C2CCNCC2)C1=O.Cl[C:41]1[N:50]=[CH:49][C:48]2[C:43](=[CH:44][C:45]([Cl:51])=[CH:46][CH:47]=2)[N:42]=1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.O>[Cl:51][C:45]1[CH:44]=[C:43]2[C:48]([CH:49]=[N:50][C:41]([N:15]3[CH2:16][CH2:17][CH:12]([N:5]4[C:6]5=[N:7][CH:8]=[CH:9][N:10]=[C:11]5[C:3]([CH3:19])([CH3:2])[C:4]4=[O:18])[CH2:13][CH2:14]3)=[N:42]2)=[CH:47][CH:46]=1

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 7,7-dimethyl-5-(piperidin-4-yl)-5H-pyrrolo[2,3-b]pyrazin-6(7H)-one hydrochloride (Intermediate 78) (0.150 g, 0.530 mmol, Intermediate 57), 2,7-dichloroquinazoline (0.127 g, 0.637 mmol), and potassium carbonate (0.257 g, 1.857 mmol) in DMSO (3 mL) was heated at 110° C. in 2 h. The reaction mixture was cooled, H2O was added, and the solid was collected, purified by ISCO (30% EtOAc/Hexanes) to give the title compound (165 mg, 76%). MS (M+1): 409. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.25 (1 H, s), 8.08 (1 H, d, J=3.1 Hz), 8.12 (1 H, d, J=3.1 Hz), 7.89 (1 H, d, J=8.6 Hz), 7.54 (1 H, d, J=1.8 Hz), 7.29 (1 H, dd, J=8.6, 2.0 Hz), 5.02 (2 H, d, J=13.3 Hz), 4.60 (1 H, tt, J=12.2, 4.0 Hz), 2.92-3.15 (2 H, m), 2.42 (2 H, qd, J=12.6, 4.4 Hz), 1.82 (2 H, d, J=9.8 Hz), 1.32 (6 H, s).

Workup

temperatureThe reaction mixture was cooled
customthe solid was collected
custompurified by ISCO (30% EtOAc/Hexanes)

Sources & evidence

ORD record: ord-caf009b1439b4f1881a063800311be39
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09174992B2

Reaction notes

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