2,6-Dimethylaniline → HCID 25069844, compound

HRID 2402502Notes

Reaction equation

HRID 2402502 reaction equation
[CH3:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:5]([CH3:9])[C:3]=1[NH2:4].[CH3:10][C:11]1[CH:12]=[C:13]([CH:17]=[CH:18][C:19]=1[NH:20][C:21]1[N:30]=[C:29]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[N:22]=1)[C:14](O)=[O:15].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CC(N(C)C)=O.C(OCC)(=O)C>[CH3:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:5]([CH3:9])[C:3]=1[NH:4][C:14](=[O:15])[C:13]1[CH:17]=[CH:18][C:19]([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)=[C:11]([CH3:10])[CH:12]=1

Participants

7

Reactant 4

HCID 68962,6-DimethylanilineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57662953HCID 57662953, compound

Product 1

HCID 25069844HCID 25069844, compoundYield 47%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

A stirred solution of 2,6-dimethylaniline (130 μL, 1.06 mmol), 3-methyl-4-(4-phenylquinazolin-2-ylamino)benzoic acid (188 mg, 0.53 mmol), HATU (433 mg, 1.13 mmol) and Hunig's base (350 μL, 2.00 mmol) in dimethylacetamide (10 mL) was heated to 70° C. overnight. The reaction mixture was diluted with ethyl acetate (100 mL) and extracted with a 10% aqueous solution of lithium chloride and a 1 N solution of sodium hydroxide. The combined organic phases were dried over sodium sulfate, filtered and concentrated on a rotary evaporator. The product was purified by preparative reverse phase HPLC (CH3CN/H2O). Acetonitrile was removed from the isolated pure fractions on a rotary evaporator and the aqueous remainder was lyophilized to give N-(2,6-dimethylphenyl)-3-methyl-4-[(4-phenylquinazolin-2-yl)amino]benzamide as a white solid (114 mg, 47%). 1H NMR (400 MHz, DMSO-d6): δ 9.68 (s, 1H), 9.20 (s, 1H), 8.03 (m, 1H), 7.88 (m, 2H), 7.80 (m, 2H), 7.78 (m, 2H), 7.65 (m, 4H), 7.35 (m, 1H), 7.13 (m, 3H), 2.40 (s, 3H), 2.20 (s, 6H). MS (EI) for C30H26N4O: 459.0 (MH+).

Workup

  1. extractionextracted with a 10% aqueous solution of lithium chloride
  2. dry with materialThe combined organic phases were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated on a rotary evaporator
  5. customThe product was purified by preparative reverse phase HPLC (CH3CN/H2O)
  6. customAcetonitrile was removed from the isolated pure fractions on a rotary evaporator

Sources & evidence

ORD record
ord-cf3b4912f4ca42e9915038d03e37bc2d
Source dataset
uspto-grants-2014_08
Patent number
US08796294B2

Reaction notes

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