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

HRID 76528Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6](Cl)[C:5]([F:9])=[CH:4][N:3]=1.[C:10]([O:14][C:15]([NH:17][C:18]1[CH:19]=[C:20]([CH:22]=[CH:23][CH:24]=1)[NH2:21])=[O:16])([CH3:13])([CH3:12])[CH3:11]>CO.O>[C:10]([O:14][C:15]([NH:17][C:18]1[CH:19]=[C:20]([NH:21][C:2]2[N:7]=[C:6]([NH:21][C:20]3[CH:22]=[CH:23][CH:24]=[C:18]([NH:17][C:15]([O:14][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:16])[CH:19]=3)[C:5]([F:9])=[CH:4][N:3]=2)[CH:22]=[CH:23][CH:24]=1)=[O:16])([CH3:13])([CH3:11])[CH3:12]

Participants

Conditions

Temperature: 70 °C

Procedure

2,4-Dichloro-5-fluoropyrimidine (75 mg, 0.45 mmol) was dissolved in a mixture of MeOH (2 ml) and H2O (0.2 ml). 3-tert-butoxycarbonylaminoaniline (374 mg, 1.8 mmol) was added and the mixture was refluxed for 40 hours (70° C. oil-bath temperature). The mixture was cooled to 22° C., concentrated to dryness under reduced pressure and subjected to column chromatography on silica gel (CHCl3-Acetone, 9:1) to give N2,N4-bis[3-(tert-butoxycarbonylamino)phenyl]-5-fluoro-2,4-pyrimidinediamine. 1H NMR (DMSO-d6+CD3OD): δ 7.96 (d, 1H, J=4.1 Hz), 7.83 (m, 1H), 7.60 (m, 1H), 7.34-7.42 (m, 2H), 7.15-7.19 (m, 2H), 7.06 (t, 1H, J=8.2 Hz), 6.93 (d, 1H, J=8.2 Hz), 1.43 (s, 9H), 1.40 (s, 9H); LCMS: purity: 93.2%; MS (m/e): 511.06 (M+, 100).

Workup

temperatureThe mixture was cooled to 22° C.
concentrationconcentrated to dryness under reduced pressure

Sources & evidence

ORD record: ord-d9b7c8d668174fcdab9e72cbee1a11a2
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835430B2

Reaction notes

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