p-Toluenesulfonic acid → 4-(6-bromo-1H-benzo[d]imidazol-1-yl)pyrimidin-2-amine

HRID 1398504Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][C:3]=1[NH:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]([NH2:16])[N:11]=1.[CH:17](OC)(OC)OC.CC1C=CC(S(O)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>C1COCC1.CO>[Br:8][C:5]1[CH:6]=[CH:7][C:2]2[N:1]=[CH:17][N:9]([C:10]3[CH:15]=[CH:14][N:13]=[C:12]([NH2:16])[N:11]=3)[C:3]=2[CH:4]=1

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of 4-N-(2-amino-5-bromophenyl)pyrimidine-2,4-diamine (750 mg, 2.68 mmol) in mixture of methanol (7 mL) and THF (30 mL) was added trimethyl orthoformate (8.81 ml, 80.32 mmol) and TsOH (0.04 ml, 0.27 mmol). The reaction mixture was stirred at 70° C. for 1 h. Then another portion of trimethyl orthoformate (4.4 ml, 40.16 mmol) was added. Stirring at 70° C. was continued for another 6 hr. The reaction mixture was allowed to cool down to RT then a saturated aqueous solution of NaHCO3 was added. The product was extracted into DCM (×3) and the combined organic layers were washed with brine and dried over Na2SO4, filtered and concentrated in vacuo to give the title compound; 1H NMR (500 MHz, DMSO) δ 7.08-7.24 (3H, m), 7.50 (1H, dd, J=8.51, 1.89 Hz), 7.71 (1H, d, J=8.51 Hz), 8.37 (1H, d, J=5.52 Hz), 8.83 (1H, d, J=1.73 Hz), 9.08 (1 H, s); LC-MS (Method B): m/z=+289.9, 291.8 (M+H)+. This compound, with LC-MS purity=70%, was used in the next step without further purification.

Workup

stirringStirring at 70° C.
waitwas continued for another 6 hr
temperatureto cool down to RT
extractionThe product was extracted into DCM (×3)
washthe combined organic layers were washed with brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-95ea796a0a154b68adcc9f65f8244992
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901313B2

Reaction notes

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