2-(4-((5-(2-(4-Chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenoxy)ethanamine hydrochloride → HCID 178490000, compound

HRID 1627305Notes

Reaction equation

HRID 1627305 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([C:12]2[N:16]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[C:15]([S:24][CH2:25][C:26]3[C:35]([F:36])=[CH:34][C:29]([O:30][CH2:31][CH2:32][NH2:33])=[CH:28][C:27]=3[F:37])=[N:14][CH:13]=2)([CH3:11])[CH3:10])=[CH:5][C:4]=1[O:38][CH3:39].[N-:40]([C:43]#[N:44])[C:41]#[N:42]>C(O)(C)C>[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([C:12]2[N:16]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[C:15]([S:24][CH2:25][C:26]3[C:27]([F:37])=[CH:28][C:29]([O:30][CH2:31][CH2:32][NH:33]/[C:43](/[NH2:44])=[N:40]/[C:41]#[N:42])=[CH:34][C:35]=3[F:36])=[N:14][CH:13]=2)([CH3:11])[CH3:10])=[CH:5][C:4]=1[O:38][CH3:39]

Participants

4

Reactant 2

HCID 667399852-(4-((5-(2-(4-Chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenoxy)ethanamine hydrochlorideHCID 178512229HCID 178512229, compound

Product 1

HCID 178490000HCID 178490000, compoundYield 57.1%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To a solution of 2-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenoxy)ethanamine hydrochloride (100 mg, 0.167 mmol) in isopropylalcohol (5 mL) was added dicyanamide (19.3 mg, 0.217 mmol) and the reaction mixture was heated at reflux for 24 h. Solvent was evaporated in vacuo and the residue was purified by column chromatography (CH2Cl2/MeOH=20:1) to give the title compound (60 mg, 57%) as an ivory solid. 1H NMR (400 MHz, CD3OD) δ 7.22 (s, 1H), 7.17 (d, J=8.2 Hz, 1H), 6.77 (t, J=8.43 Hz, 2H), 6.60-6.42 (m, 5H), 6.25 (dd, J=7.8, 4.7 Hz, 2H), 4.02 (t, J=4.54 Hz, 2H), 3.83 (s, 2H), 3.71 (s, 3H), 3.56 (t, J=4.65 Hz, 2H), 3.51-3.41 (m, 1H), 1.49 (s, 6H), 1.20 (d, J=44.2 Hz, 3H), 0.93-0.80 (m, 1H); MS (EI) m/z 629 (MH+).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 24 h
  3. customSolvent was evaporated in vacuo
  4. customthe residue was purified by column chromatography (CH2Cl2/MeOH=20:1)

Sources & evidence

ORD record
ord-5b8efb379d8b48a29e8ac069d237cf8c
Source dataset
uspto-grants-2014_07
Patent number
US08785488B2

Reaction notes

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