p-Toluenesulfonic acid → 4-(6-bromo-2-methyl-1H-1,3-benzodiazol-1-yl)pyrimidin-2-amine

HRID 1398507Notes

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.[C:17](OC)(OC)(OC)[CH3:18].CC1C=CC(S(O)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>CO.C1COCC1>[Br:8][C:5]1[CH:6]=[CH:7][C:2]2[N:1]=[C:17]([CH3:18])[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 (300 mg, 1.07 mmol) in a mixture of methanol (5 mL) and THF (20 mL) was added trimethyl orthoacetate (2.02 ml, 0.02 mol) and TsOH (0.02 ml, 0.11 mmol). The reaction mixture was stirred at 70° C. for 40 min then allowed to stand at RT for 3 days. A saturated aqueous solution of NaHCO3 was added. The product was extracted into DCM (×3) and the organic layers were washed with brine and then dried with Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography (Isolute column, 1-2% MeOH in DCM) to give the title compound as a yellow solid; 1H NMR (500 MHz, DMSO) δ 2.67 (3H, s), 6.88 (1H, d, J=5.20 Hz), 7.13 (2H, br. s.), 7.41 (1H, dd, J=8.51, 1.89 Hz), 7.58 (1H, d, J=8.51 Hz), 7.86 (1H, d, J=1.89 Hz), 8.48 (1H, d, J=5.20 Hz); LC-MS: m/z=+303.9, 305.7 (M+H)+.

Workup

waitto stand at RT for 3 days
extractionThe product was extracted into DCM (×3)
washthe organic layers were washed with brine
dry with materialdried with Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by flash chromatography (Isolute column, 1-2% MeOH in DCM)

Sources & evidence

ORD record: ord-883d5aef1b0f4d1699235185714514a3
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901313B2

Reaction notes

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