Methylamine → HCID 22484252, compound

HRID 2055155Notes

Reaction equation

HRID 2055155 reaction equation
[CH3:1][NH:2]C(=O)N.C1([O:12][C:13](=O)[NH:14][CH2:15][C:16]#[C:17][C:18]2[CH:19]=[C:20]3[C:25](=[CH:26][CH:27]=2)[N:24]=[CH:23][N:22]=[C:21]3[NH:28][C:29]2[CH:34]=[CH:33][C:32]([O:35][C:36]3[CH:37]=[N:38][C:39]([CH3:42])=[CH:40][CH:41]=3)=[C:31]([Cl:43])[CH:30]=2)C=CC=CC=1.CN>CS(C)=O>[Cl:43][C:31]1[CH:30]=[C:29]([NH:28][C:21]2[C:20]3[C:25](=[CH:26][CH:27]=[C:18]([C:17]#[C:16][CH2:15][NH:14][C:13]([NH:2][CH3:1])=[O:12])[CH:19]=3)[N:24]=[CH:23][N:22]=2)[CH:34]=[CH:33][C:32]=1[O:35][C:36]1[CH:37]=[N:38][C:39]([CH3:42])=[CH:40][CH:41]=1

Participants

5

Reactant 3

HCID 6329MethylamineHCID 11719MethylureaHCID 69115944HCID 69115944, compound

Product 1

HCID 22484252HCID 22484252, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

1-{4-[3-Chloro-4-(6-methyl-pyridin-3-yloxy)-phenylamino]-quinazolin-6-yl}-prop-2-ynyl)-3-methyl-urea: 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

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

Sources & evidence

ORD record
ord-5108be7cb05f4ac480299ec6142fef26
Source dataset
uspto-grants-2008_02
Patent number
US07332493B2

Reaction notes

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