Ammonia → 4-(5-Iodo-1H-pyrazol-4-yl)-2-(methylsulfanyl)pyrimidine

HRID 500709Notes

Reaction equation

N([O-])=O.[Na+].[CH3:5][S:6][C:7]1[N:12]=[C:11]([C:13]2[CH:14]=[N:15][NH:16][C:17]=2N)[CH:10]=[CH:9][N:8]=1.OS(O)(=O)=O.[I-:24].[K+].N.II.[O-]S([O-])(=S)=O.[Na+].[Na+]>O.C(O)(=O)C>[I:24][C:17]1[NH:16][N:15]=[CH:14][C:13]=1[C:11]1[CH:10]=[CH:9][N:8]=[C:7]([S:6][CH3:5])[N:12]=1

Participants

Conditions

Temperature: -1 °C

Procedure

A solution of NaNO2 (20.0 g, 0.29 mol) in water (150 mL) was poured into a solution of 4-(2-(methylthio)pyrimidin-4-yl)-1H-pyrazol-5-amine 6 (50.0 g, 0.24 mol) in a mixture of glacial acetic acid (400 mL) and water (100 mL) at −3° C. The temperature increased to −1° C. Concentrated H2SO4 (10 mL) was added to the obtained solution, and a solution of potassium iodide (120.0 g, 1.2 mol.) and 12 (123.0 g, 10.48 mol) in water (200 mL) was added dropwise. The obtained solution was heated to 50° C. for 2 h, and the mixture was neutralized with aqueous ammonia. Excess iodine was treated with Na2S2O3. The precipitate was filtered, and the filtrate was extracted with ethyl acetate. The organic layer was evaporated, and the residue was purified by chromatography (THF: EtOAc=4:1) to give 4-(5-iodo-1H-pyrazol-4-yl)-2-(methylthio)pyrimidine (A) (42.2 g, 54.6%) as a yellow solid. 1H NMR (400 MHz, DMSO): δ 8.55 (d, 1H), 8.35 (s, 1H), 7.55 (d, 1H), 2.55 (s, 3H).

Workup

temperatureThe obtained solution was heated to 50° C. for 2 h
filtrationThe precipitate was filtered
extractionthe filtrate was extracted with ethyl acetate
customThe organic layer was evaporated
customthe residue was purified by chromatography (THF: EtOAc=4:1)

Sources & evidence

ORD record: ord-2dd573ccc0034fd0a43dd16ed250d0db
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07772246B2

Reaction notes

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