Methanamine, N-methoxy-, hydrochloride (1:1) → N,4-dimethyl-N-(methyloxy)-3-[({4-[(4-phenylquinazolin-2-yl)amino]phenyl}carbonyl)amino]benzamide

HRID 406819Notes

Reaction equation

HRID 406819 reaction equation
[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[NH:11][C:12]([C:14]1[CH:19]=[CH:18][C:17]([NH:20][C:21]2[N:30]=[C:29]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[N:22]=2)=[CH:16][CH:15]=1)=[O:13].Cl.[CH3:38][NH:39][O:40][CH3:41].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O.ClCCl>[CH3:38][N:39]([O:40][CH3:41])[C:6](=[O:8])[C:5]1[CH:9]=[CH:10][C:2]([CH3:1])=[C:3]([NH:11][C:12]([C:14]2[CH:15]=[CH:16][C:17]([NH:20][C:21]3[N:30]=[C:29]([C:28]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:31]4[C:36](=[CH:35][CH:34]=[CH:33][CH:32]=4)[N:22]=3)=[CH:18][CH:19]=2)=[O:13])[CH:4]=1

Participants

7

Reactant 4

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 250701624-Methyl-3-[({4-[(4-phenylquinazolin-2-yl)amino]phenyl}carbonyl)amino]benzoic acid

Product 1

HCID 25070163N,4-dimethyl-N-(methyloxy)-3-[({4-[(4-phenylquinazolin-2-yl)amino]phenyl}carbonyl)amino]benzamideYield 97%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 4-methyl-3-[({4-[(4-phenylquinazolin-2-yl)amino]phenyl}carbonyl)-amino]benzoic acid (1.10 g, 2.32 mmol), N,O-dimethylhydroxylamine hydrochloride (226 mg, 2.32 mmol), and Hunig's base (1.62 mL, 9.30 mmol) in dimethylformamide (15 mL) were added HATU (882 mg, 2.32 mmol) and the mixture was stirred at rt for 2 h. The mixture was diluted with dichloromethane and washed with 2 N sodium hydroxide. The separated organic layer was dried over sodium sulfate, concentrated on a rotary evaporator and the residue was purified by short flash column chromatography to give N,4-dimethyl-N-(methyloxy)-3-[({4-[(4-phenylquinazolin-2-yl)amino]phenyl}carbonyl)amino]benzamide (1.16 g, 97%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 10.34 (s, 1H), 9.80 (s, 1H), 8.19 (d, 2H), 8.00 (d, 2H), 7.90-7.79 (m, 5H), 7.67-7.63 (m, 4H), 7.44-7.40 (m, 2H), 7.35 (d, 1H), 3.59 (s, 3H), 3.27 (s, 3H), 2.31 (s, 3H). MS (EI) for C31H27N5O3: 518.3 (MH+).

Workup

  1. washwashed with 2 N sodium hydroxide
  2. dry with materialThe separated organic layer was dried over sodium sulfate
  3. concentrationconcentrated on a rotary evaporator
  4. customthe residue was purified by short flash column chromatography

Sources & evidence

ORD record
ord-988df74a05b740c8a43eb25ee19c3e4f
Source dataset
uspto-grants-2014_06
Patent number
US08754092B2

Reaction notes

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