Cyclopropyl isothiocyanate → 3-Cyclopropyl-1-[2-(5-fluoro-pyridin-3-yl)-4-methyl-thiazol-5-yl]-1-methyl-thiourea

HRID 1470429Notes

Reaction equation

HRID 1470429 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[S:9][C:10]([NH:14][CH3:15])=[C:11]([CH3:13])[N:12]=2)[CH:5]=[N:6][CH:7]=1.[N:16]([CH:19]1[CH2:21][CH2:20]1)=[C:17]=[S:18]>O1CCOCC1>[CH:19]1([NH:16][C:17](=[S:18])[N:14]([C:10]2[S:9][C:8]([C:4]3[CH:5]=[N:6][CH:7]=[C:2]([F:1])[CH:3]=3)=[N:12][C:11]=2[CH3:13])[CH3:15])[CH2:21][CH2:20]1

Participants

4

Reactant 2

HCID 92463Cyclopropyl isothiocyanateHCID 666453412-(5-fluoropyridin-3-yl)-N,4-dimethylthiazol-5-amine

Product 1

HCID 595804973-Cyclopropyl-1-[2-(5-fluoro-pyridin-3-yl)-4-methyl-thiazol-5-yl]-1-methyl-thioureaYield 73%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of 2-(5-fluoropyridin-3-yl)-N,4-dimethylthiazol-5-amine (200 mg, 0.896 mmol) and isothiocyanatocyclopropane (266 mg, 2.69 mmol) in dioxane (10 mL) was heated at 100° C. for 24 h before the solvent was removed under reduced pressure. The residue was purified via silica gel chromatography (0 to 100% ethyl acetate/hexanes) to afford the title compound as a yellow solid (211 mg, 73%): mp 117-119° C.; 1H NMR (400 MHz, CDCl3) δ 8.89 (s, 1H), 8.56 (d, J=2.8 Hz, 1H), 7.96 (dt, J=9.2 Hz, 2.4 Hz, 1H), 5.91 (br s, 1H), 3.62 (s, 3H), 3.04-2.99 (m, 1H), 2.31 (s, 3H), 0.89-0.81 (m, 2H), 0.57-0.48 (m, 2H); ESIMS m/z 323 (M+1).

Workup

  1. customwas removed under reduced pressure
  2. customThe residue was purified via silica gel chromatography (0 to 100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-7b7816bb20a64bad8ec20235c7334283
Source dataset
uspto-grants-2015_04
Patent number
US09006446B2

Reaction notes

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