4-Aminobenzoic Acid → HCID 25073934, compound

HRID 2402505Notes

Reaction equation

HRID 2402505 reaction equation
Cl[C:2]1[N:11]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[NH2:18][C:19]1[CH:27]=[CH:26][C:22]([C:23]([OH:25])=O)=[CH:21][CH:20]=1.[CH3:28][N:29]([CH2:31][C:32]1[CH:33]=[CH:34][C:35]([CH3:39])=[C:36]([CH:38]=1)[NH2:37])[CH3:30].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>C(O)CCC.C(OCC)(=O)C>[CH3:30][N:29]([CH2:31][C:32]1[CH:33]=[CH:34][C:35]([CH3:39])=[C:36]([NH:37][C:23](=[O:25])[C:22]2[CH:21]=[CH:20][C:19]([NH:18][C:2]3[N:11]=[C:10]([C:12]4[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=4)[C:9]4[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=4)[N:3]=3)=[CH:27][CH:26]=2)[CH:38]=1)[CH3:28]

Participants

8

Reactant 5

HCID 9784-Aminobenzoic AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 13774682HCID 13774682, compoundHCID 59595940HCID 59595940, compound

Product 1

HCID 25073934HCID 25073934, compoundYield 31.9%

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 2-chloro-4-(pyridin-2-yl)quinazoline (60 mg, 0.25 mmol) in butanol was added 4-aminobenzoic acid (36 mg, 0.26 mmol) and the stirred mixture was heated to reflux for 20 min, after which time the reaction mixture was cooled and the solvent removed on a rotary evaporator. The residue was redissolved in dimethylformamide (20 mL) and 5-((dimethyl-amino)methyl)-2-methylaniline (50 mg, 0.30 mmol), HATU (170 mg, 0.45 mmol) and Hunig's base (150 μL, 0.87 mmol) were added to the solution. The stirred mixture was heated to 70° C. for 18 h, then diluted with ethyl acetate and the solution was extracted with 10% aqueous lithium chloride and 1 N hydrochloric acid. The combined acidic washes were made basic with saturated sodium bicarbonate and extracted with ethyl acetate. The combined organic extracts were then dried over sodium sulfate, filtered and concentrated on a rotary evaporator. The product was purified by preparative reverse phase HPLC to give N-{5-[(dimethylamino)methyl]-2-methylphenyl}-4-[(4-pyridin-2-ylquinazolin-2-yl)amino]benzamide as a yellow solid (39 mg, 16% yield). 1H-NMR (400 MHz, DMSO-d6): δ11.30 (s, 1H), 10.30 (s, 1H), 9.68 (s, 1H), 8.84-8.83 (m, 1H), 8.49-8.47 (d, 1H), 8.16-8.09 (m, 3H), 8.16-8.09 (m, 2H), 7.99-7.97 (m, 2H), 7.43-7.39 (m, 1H), 7.37 (s, 1H), 7.21 (d, 2H), 7.07 (d, 1H), 3.43 (br s, 2H), 2.22 (s, 6H), 2.20 (s, 3H). MS (EI) for C30H28N6O: 489.3 (MH+).

Workup

  1. temperaturethe stirred mixture was heated
  2. temperatureto reflux for 20 min
  3. temperatureafter which time the reaction mixture was cooled
  4. customthe solvent removed on a rotary evaporator
  5. dissolutionThe residue was redissolved in dimethylformamide (20 mL)
  6. extractionthe solution was extracted with 10% aqueous lithium chloride and 1 N hydrochloric acid
  7. extractionextracted with ethyl acetate
  8. dry with materialThe combined organic extracts were then dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated on a rotary evaporator
  11. customThe product was purified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-5017515f3a5c478484739d41e4b13673
Source dataset
uspto-grants-2014_08
Patent number
US08796294B2

Reaction notes

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