Ethanol → HCID 86632603, compound

HRID 2076019Notes

Reaction equation

HRID 2076019 reaction equation
CO[C:3]1[CH:4]=[C:5]([NH:15][C:16]([NH2:18])=[S:17])[CH:6]=[CH:7][C:8]=1[N:9]1[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10]1.Br.BrC1[C:26](=O)[CH:25]([C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[C:30]([F:35])[CH:29]=2)[CH2:24][CH2:23][CH2:22]1.C([N:39]([CH2:43][CH3:44])C(C)C)(C)C.[CH2:45]([OH:47])C>>[CH2:43]([N:39]1[CH2:26][CH:25]([C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[C:30]([F:35])[CH:29]=2)[C:24]2[N:18]=[C:16]([NH:15][C:5]3[CH:4]=[CH:3][C:8]([N:9]4[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10]4)=[CH:7][C:6]=3[O:47][CH3:45])[S:17][C:23]=2[CH2:22]1)[C:44]1[CH:5]=[CH:4][CH:3]=[CH:8][CH:7]=1

Participants

5

Reactant 4

HCID 702EthanolHCID 81531DiisopropylethylamineHCID 67096224HCID 67096224, compoundHCID 71650841[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]thiourea

Product 1

HCID 86632603HCID 86632603, compoundYield 6%

Procedure

A suspension of [3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-thiourea (100 mg, 0.38 mmol) and of crude 6-bromo-2-(4-chloro-3-fluorophenyl)-cyclohexanone hydrobromide (147 mg, 0.31 mmol) in ethanol (5 mL) was heated to reflux under an atmosphere of nitrogen for 2 days. N,N-diisopropyl ethyl amine (49 mg, 0.38 mmol) was added and the reaction was heated to reflux over night. After cooling to room temperature the solvent was evaporated under reduced pressure and the residue was treated with dichloromethane/methanol/concentrated aqueous NH4OH solution (9:1:0.1 v/v/v). The precipitate was filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by reversed preparative HPLC using acetonitril/water (0.1% formic acid) to yield the title compound (12 mg, 6%) as a yellow solid. MS ISP (m/e): 559.8/561.8 (100/45) [(M+H)+]. 1H NMR (CDCl3, 300 MHz): δ (ppm)=7.70 (s, 1H), 7.29 (m, 7H), 7.12 (s, 1H), 7.09 (s, 1H), 7.03 (d, 1H), 6.82 (s, 1H), 6.72 (d, 1H), 4.08 (m, 1H), 3.73 (m, 3H), 3.66 (s, 1H), 3.58 (d, 1H), 3.12 (dd, 1H), 2.73 (dd, 1H), 2.29 (s, 3H).

Workup

  1. temperatureto reflux under an atmosphere of nitrogen for 2 days
  2. temperaturethe reaction was heated
  3. temperatureto reflux over night
  4. customwas evaporated under reduced pressure
  5. additionthe residue was treated with dichloromethane/methanol/concentrated aqueous NH4OH solution (9:1:0.1 v/v/v)
  6. filtrationThe precipitate was filtered off
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe residue was purified by reversed preparative HPLC

Sources & evidence

ORD record
ord-7613df4dbf3447059690852ba05a19a7
Source dataset
uspto-grants-2011_04
Patent number
US07923450B2

Reaction notes

Loading…