4-Aminobenzoic Acid → N2,N4-bis(4-carboxyphenyl)-5-fluoro-2,4-pyrimidinediamine

HRID 2278032Notes

Reaction equation

HRID 2278032 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1.Cl[C:12]1[N:17]=[C:16](Cl)[C:15]([F:19])=[CH:14][N:13]=1>CO.O>[C:6]([C:5]1[CH:9]=[CH:10][C:2]([NH:1][C:12]2[N:17]=[C:16]([NH:1][C:2]3[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=3)[C:15]([F:19])=[CH:14][N:13]=2)=[CH:3][CH:4]=1)([OH:8])=[O:7]

Participants

5

Reactant 2

HCID 9784-Aminobenzoic AcidHCID 2507052,4-Dichloro-5-fluoropyrimidine

Product 1

HCID 22060467N2,N4-bis(4-carboxyphenyl)-5-fluoro-2,4-pyrimidinediamine

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-Aminobenzoic acid (410 mg, 3 mmol) and 2,4-dichloro-5-fluoropyrimidine (100 mg, 0.6 mmol) in methanol (10 mL) and water (1 mL) was stirred at 100° C. for 24 h to yield N2,N4-bis(4-carboxyphenyl)-5-fluoro-2,4-pyrimidinediamine after methanol was removal. This residue was redissolved in DMF (10 mL) and to it was added potassium carbonate (1.65 g, 12 mmol) and iodomethane (0.37 mL, 6 mmol), stirred at room temperature overnight, and then diluted with 1 N HCl (80 mL) and ethyl acetate (80 mL). The ethyl acetate layer was washed with 1N HCl (60 mL) and water (60 mL). The organic layer was separated, dried, evaporated and the resulting residue was recrystallized from ethyl acetate/hexanes to give N2,N4-bis(4-methoxycarbonylphenyl)-5-fluoro-2,4-pyrimidinediamine (150 mg, 63%). 1H NMR (acetone-d6): δ 3.85 (s, 3H), 3.88 (s, 3H), 7.88-7.97 (m, 4H), 7.98-8.05 (m, 4H), 8.18 (d, J=3.0 Hz, 1H), 9.00 (br, 1H, NH), 9.04 (br, 1H, NH); LCMS: ret. time: 27.07 min.; purity: 95.54%; MS (m/e): 397.04 (MH+).

Sources & evidence

ORD record
ord-f6d994c168da46869203d40cabd3d57a
Source dataset
uspto-grants-2015_09
Patent number
US09133133B2

Reaction notes

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