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

HRID 76641

Reaction equation

HRID 76641 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-16d1d672096e438c82c85a742a3a50ed
Source dataset
uspto-grants-2014_09
Patent number
US08835430B2

Linked notes

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