2,4-Dichloro-5-fluoropyrimidine → N2,N4-bis[3-(ethylaminocarbonylamino)phenyl]-5-fluoro-2,4-pyrimidinediamine

HRID 2278036Notes

Reaction equation

HRID 2278036 reaction equation
[CH2:1]([NH:3][C:4]([NH:6][C:7]1[CH:8]=[C:9]([CH:11]=[CH:12][CH:13]=1)[NH2:10])=[O:5])[CH3:2].Cl[C:15]1[N:20]=[C:19](Cl)[C:18]([F:22])=[CH:17][N:16]=1>>[CH2:1]([NH:3][C:4]([NH:6][C:7]1[CH:8]=[C:9]([NH:10][C:15]2[N:20]=[C:19]([NH:10][C:9]3[CH:11]=[CH:12][CH:13]=[C:7]([NH:6][C:4]([NH:3][CH2:1][CH3:2])=[O:5])[CH:8]=3)[C:18]([F:22])=[CH:17][N:16]=2)[CH:11]=[CH:12][CH:13]=1)=[O:5])[CH3:2]

Participants

3

Reactant 2

HCID 2507052,4-Dichloro-5-fluoropyrimidineHCID 220611881-(3-Aminophenyl)-3-ethylurea

Product 1

HCID 22060703N2,N4-bis[3-(ethylaminocarbonylamino)phenyl]-5-fluoro-2,4-pyrimidinediamineYield 66.3%

Procedure

In a manner analogous to the preparation of N2,N4-bis[4-(ethylaminocarbonylamino)phenyl]-5-fluoro-2,4-pyrimidinediamine, the reaction of 1,3-diaminobenzene (2 g, 18.5 mmol), ethyl isocyanate (0.5 mL, 6.3 mmol) and potassium carbonate (4.36 g, 31.5 mmol) gave 3-(ethylaminocarbonylamino)aniline (940 mg, 83%). The reaction of 3-(ethylaminocarbonylamino)aniline (537 mg, 3 mmol) and 2,4-dichloro-5-fluoropyrimidine (100 mg, 0.6 mmol) gave N2,N4-bis[3-(ethylaminocarbonylamino)phenyl]-5-fluoro-2,4-pyrimidinediamine (180 mg, 66%) as a white solid. 1H NMR (CD3OD): δ 1.14 (t, J=6.9 Hz, 3H), 1.15 (t, J=7.5 Hz, 3H), 3.21 (q, J=7.2 Hz, 2H), 3.22 (q, J=7.5 Hz, 2H), 7.06 (ddd, J=0.9, 2.1, 7.8 Hz, 1H), 7.10-7.28 (m, 5H), 7.53 (t, J=2.1 Hz, 1H), 7.80 (m, 1H), 7.92 (d, J=5.7 Hz, 1H); LCMS: ret. time: 17.17 min.; purity: 89.63%; MS (m/e): 453.38 (MH+).

Sources & evidence

ORD record
ord-c765f0385a9f440b97e7fddf7f462334
Source dataset
uspto-grants-2015_09
Patent number
US09133133B2

Reaction notes

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