Isopropyl iodide → 1-isopropyl-4-(2-(methylthio)pyrimidin-4-yl)-1H-pyrazol-3-amine

HRID 629486Notes

Reaction equation

[CH3:1][S:2][C:3]1[N:8]=[C:7]([C:9]2[C:10]([NH2:14])=[N:11][NH:12][CH:13]=2)[CH:6]=[CH:5][N:4]=1.I[CH:16]([CH3:18])[CH3:17].C[O-].[Na+]>C1COCC1>[CH:16]([N:12]1[CH:13]=[C:9]([C:7]2[CH:6]=[CH:5][N:4]=[C:3]([S:2][CH3:1])[N:8]=2)[C:10]([NH2:14])=[N:11]1)([CH3:18])[CH3:17]

Participants

Conditions

Temperature: 50 °C

Procedure

Intermediate 4-(2-(Methylthio)pyrimidin-4-yl)-1H-pyrazol-3-amine (10.0 g, 40 mmol) was dissolved in THF (200 mL), followed by addition of 2-iodopropane (6.3 mL, 63 mmol) and sodium methoxide (25% weight solution in methanol, 14.3 ml, 63 mmol). The mixture was heated at 50° C. with stirring under a nitrogen atmosphere for 3 d, then was concentrated under vacuum. The residue was taken up in ethyl acetate (200 mL) and washed with aqueous potassium carbonate solution and brine, then dried over sodium sulfate, filtered, and concentrated to provide a brown residue. The residue was chromatographed on silica gel (hexane/ethyl acetate eluant) to provide 1-isopropyl-4-(2-(methylthio)pyrimidin-4-yl)-1H-pyrazol-3-amine as a solid; 1H NMR 400 MHz (CDCl3) δ 8.23 (d, J=5.6 Hz, 1H), 7.60 (s, 1H), 6.83 (d, J=5.6 Hz, 1H), 5.23 (d, J=2.8 Hz, 2H), 4.21-4.25 (m, 1H), 2.50 (s, 3H), 1.37 (d, J=6.8 Hz, 6H); MS m/z: 250.1 (M+1).

Workup

concentrationwas concentrated under vacuum
washwashed with aqueous potassium carbonate solution and brine
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customto provide a brown residue
customThe residue was chromatographed on silica gel (hexane/ethyl acetate eluant)

Sources & evidence

ORD record: ord-858fb5ae46e842c8a1616860837a83af
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09314464B2

Reaction notes

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