Methylamine → HCID 22484252, compound

HRID 2180977Notes

Reaction equation

C1([O:7][C:8](=O)[NH:9][CH2:10][C:11]#[C:12][C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][CH:22]=2)[N:19]=[CH:18][N:17]=[C:16]3[NH:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][C:31]3[CH:32]=[N:33][C:34]([CH3:37])=[CH:35][CH:36]=3)=[C:26]([Cl:38])[CH:25]=2)C=CC=CC=1.[CH3:40][NH2:41]>CS(C)=O>[Cl:38][C:26]1[CH:25]=[C:24]([NH:23][C:16]2[C:15]3[C:20](=[CH:21][CH:22]=[C:13]([C:12]#[C:11][CH2:10][NH:9][C:8]([NH:41][CH3:40])=[O:7])[CH:14]=3)[N:19]=[CH:18][N:17]=2)[CH:29]=[CH:28][C:27]=1[O:30][C:31]1[CH:32]=[N:33][C:34]([CH3:37])=[CH:35][CH:36]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of (3-{4-[3-Chloro-4-(6-methyl-pyridin-3-yloxy)-phenylamino]-quinazolin-6-yl}-prop-2-ynyl)-carbamic acid phenyl ester (0.1 g, 0.18 mmol) prepared by Method B, methyl amine (2.0M methanol solution, 1 mL, 2 mmol) and DMSO (0.5 mL) was stirred at 80° C. overnight. The solvents were removed under vacuum (GeneVac HT-8) and the residue was re-dissolved in MeOH (˜1 mL). HCl gas was bubbled through the solution and EtOAc resulting in precipitation of the desired product. The title compound (80 mg, 90% yield) was obtained by filtration as a yellow solid. 1HNMR (400 MHz, CD3OD) δ 2.72 (3H,s), 2.76 (3H, s), 4.19 (2H, s), 7.49 (1H, d, J=9 Hz), 7.84 (1H, d, J=2 Hz), 7.86 (1H, d, J=2 Hz), 7.92 (1H, d, J=9 Hz), 8.12 (2H, m, J=2 Hz), 8.16 (1H, d, J=2.4 Hz), 8.60 (1H, d, J=3.2 Hz), 8.74 (1H, d, J=1.2 Hz), 8.87 (1H, s ). LRMS (M+): 473.0, 475.0, 476.0.

Workup

customThe solvents were removed under vacuum (GeneVac HT-8)
dissolutionthe residue was re-dissolved in MeOH (˜1 mL)
customHCl gas was bubbled through the solution and EtOAc resulting in precipitation of the desired product

Sources & evidence

ORD record: ord-ecbfd732a7944ea9b4556e8422deb4f1
Source dataset: uspto-grants-2005_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06890924B2

Reaction notes

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