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

HRID 2402496Notes

Reaction equation

HRID 2402496 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-5eafbeca29c14c74a85980b09c8e4b7b
Source dataset
uspto-grants-2014_08
Patent number
US08796294B2

Reaction notes

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