2,6-Dimethylaniline → HCID 57663002, compound

HRID 406848Notes

Reaction equation

HRID 406848 reaction equation
[CH:1]1([C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=[C:9]([NH:17][C:18]3[CH:26]=[CH:25][C:21]([C:22](O)=[O:23])=[CH:20][CH:19]=3)[N:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.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.[CH3:60][C:61]1[CH:67]=[CH:66][CH:65]=[C:64]([CH3:68])[C:62]=1[NH2:63]>CN(C)C=O.O>[CH:1]1([C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=[C:9]([NH:17][C:18]3[CH:19]=[CH:20][C:21]([C:22]([NH:63][C:62]4[C:64]([CH3:68])=[CH:65][CH:66]=[CH:67][C:61]=4[CH3:60])=[O:23])=[CH:25][CH:26]=3)[N:8]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]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 57663055HCID 57663055, compound

Product 1

HCID 57663002HCID 57663002, compoundYield 27%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred mixture of 4-(4-cyclohexylquinazolin-2-ylamino)benzoic acid (300 mg, 0.86 mmol), HATU (327 mg, 0.86 mmol) and Hunig's base (555 μL, 4.3 mmol) in dimethylformamide (1 mL) was added 2,6-dimethylaniline (620 mg, 5.12 mmol) and the reaction was heated to 50° C. overnight. The mixture was cooled to rt, diluted with water and extracted with ethyl acetate. The combined organic extracts were washed with 1 N sodium bicarbonate and a 5% aqueous solution of lithium chloride, then was extracted with 1 N hydrochloric acid. The combined acidic washes were neutralized with 1 N sodium hydroxide and extracted with dichloromethane. These combined organic extracts were dried over sodium sulfate, filtered and concentrated on a rotary evaporator. The residue obtained was purified by recrystallization from methanol to give 4-[(4-cyclohexylquinazolin-2-yl)amino]-N-(2,6-dimethylphenyl)benzamide as a white solid (99.8 mg, 27%). 1H NMR (400 MHz, CDCl3): δ 8.06-7.94 (m, 5H), 7.82-7.71 (m, 2H), 7.58-7.49 (br s, 1H), 7.39-7.33 (m, 2H), 7.16-7.12 (m, 3H), 3.53-3.44 (m, 1H), 2.65-2.59 (s, 5H), 2.31 (s, 6H), 2.04-1.91 (m, 4H), 1.89-1.70 (m, 3H), 1.60-1.31 (m, 3H). MS (EI) for C29H30N4O: 451.0 (MH+).

Workup

  1. temperatureThe mixture was cooled to rt
  2. extractionextracted with ethyl acetate
  3. washThe combined organic extracts were washed with 1 N sodium bicarbonate
  4. extractiona 5% aqueous solution of lithium chloride, then was extracted with 1 N hydrochloric acid
  5. extractionextracted with dichloromethane
  6. dry with materialThese combined organic extracts were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated on a rotary evaporator
  9. customThe residue obtained
  10. customwas purified by recrystallization from methanol

Sources & evidence

ORD record
ord-fd623c8065ce4db08259eb29f69165ab
Source dataset
uspto-grants-2014_06
Patent number
US08754092B2

Reaction notes

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