p-Toluenesulfonic acid → HCID 68181830, compound

HRID 1398713Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([Br:9])=[CH:4][C:3]=1[NH:10][C:11]1[CH:16]=[CH:15][N:14]=[C:13]([NH2:17])[N:12]=1.[CH:18](OC)(OC)OC.CC1C=CC(S(O)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>CO.C1COCC1>[Br:9][C:5]1[C:6]([F:8])=[CH:7][C:2]2[N:1]=[CH:18][N:10]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]([NH2:17])[N:12]=3)[C:3]=2[CH:4]=1

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of 4-N-(2-amino-5-bromo-4-fluorophenyl)pyrimidine-2,4-diamine (500 mg, 1.68 mmol) in methanol (6 mL) and THF (20 mL) was added trimethyl orthoformate (5.59 ml, 50.32 mmol) and TsOH (0.03 ml, 0.17 mmol). The reaction mixture was stirred at 70° C. for 1.5 hr. Reaction had only progressed 6% by LC-MS. Extra trimethyl orthoformate (6 mL, 54.23 mmol) was added and stirred at 70° C. for 1 hr. Reaction mixture was cooled and sat NaHCO3 (10 mL) was added. The product was extracted with DCM (3×10 mL) and the organics were washed with brine and then dried (Na2SO4), filtered and concentrated in vacuo to obtain title compound as a beige solid (500 mg, 63.8% yield); 1H NMR (500 MHz, DMSO) delta 9.17 (s, 1H), 8.97 (d, J=6.7 Hz, 1H), 8.37 (d, J=5.5 Hz, 1H), 7.81 (d, J=9.1 Hz, 1H), 7.20 (s, 2H), 7.14 (d, J=5.6 Hz, 1H); LC-MS: m/z=+309.75 (M+H)+.

Workup

customReaction
stirringstirred at 70° C. for 1 hr
customReaction mixture
temperaturewas cooled
additionwas added
extractionThe product was extracted with DCM (3×10 mL)
washthe organics were washed with brine
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-d790ba60e04b4368b9248211f05489da
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901313B2

Reaction notes

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