Toluene → 2-fluoro-5-(2-(1-(4-fluoro-3-methoxyphenyl)-2-mercapto-1H-imidazol-5-yl)propan-2-yl)benzonitrile

HRID 83885Notes

Reaction equation

HRID 83885 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:10]([CH3:28])([CH3:27])[C:11](=O)[CH2:12][NH:13][C:14]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([F:23])=[C:19]([O:24][CH3:25])[CH:18]=2)=[S:15])[CH:6]=[CH:7][C:8]=1[F:9])#[N:2].C1(C)C=CC=CC=1>CC(O)=O>[F:9][C:8]1[CH:7]=[CH:6][C:5]([C:10]([C:11]2[N:16]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[C:19]([O:24][CH3:25])[CH:18]=3)[C:14]([SH:15])=[N:13][CH:12]=2)([CH3:28])[CH3:27])=[CH:4][C:3]=1[C:1]#[N:2]

Participants

4

Reactant 2

HCID 1140TolueneHCID 866622561-(3-(3-Cyano-4-fluorophenyl)-3-methyl-2-oxobutyl)-3-(4-fluoro-3-methoxyphenyl)thiourea

Product 1

HCID 1784929902-fluoro-5-(2-(1-(4-fluoro-3-methoxyphenyl)-2-mercapto-1H-imidazol-5-yl)propan-2-yl)benzonitrileYield 65.1%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A solution of 1-(3-(3-cyano-4-fluorophenyl)-3-methyl-2-oxobutyl)-3-(4-fluoro-3-methoxyphenyl)thiourea (3.7 g, 9.17 mmol) in AcOH (50 mL) was refluxed 2 h at 110° C. After the reaction was complete, it was cooled to room temperature and co-evaporated with toluene in vacuo. The residue was purified by flash column chromatography (Hex:EA=1:3) to give 2-fluoro-5-(2-(1-(4-fluoro-3-methoxyphenyl)-2-mercapto-1H-imidazol-5-yl)propan-2-yl)benzonitrile (2.3 g, 65%) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 10.6 (bs, 1H), 7.26-7.23 (m, 1H), 7.08 (t, J=9.2 Hz, 1H), 6.96 (t, J=8.8 Hz, 1H), 6.84 (d, J=2.0 Hz, 1H), 6.25-6.25 (m, 1H), 6.17-6.15 (m, 1H), 3.59 (s, 3H), 1.51 (s, 6H).

Workup

  1. customThe residue was purified by flash column chromatography (Hex:EA=1:3)

Sources & evidence

ORD record
ord-5a20eaa4c50a4a848f70a7276c73031a
Source dataset
uspto-grants-2014_09
Patent number
US08846739B2

Reaction notes

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