Hydrochloric Acid → HCID 86630010, compound

HRID 1192883Notes

Reaction equation

HRID 1192883 reaction equation
[C:1]([C:3]1([NH:7][C:8]2[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][CH2:16][C:17]3[N:18](C(OC(C)(C)C)=O)[CH:19]=[CH:20][N:21]=3)=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4]1)#N.[N:29]([C:32]1[CH:39]=[CH:38][C:35]([C:36]#[N:37])=[C:34]([C:40]([F:43])([F:42])[F:41])[CH:33]=1)=[C:30]=[S:31].Cl.C([O-])(O)=[O:46].[Na+]>CN(C=O)C.O.CO>[NH:21]1[CH:20]=[CH:19][N:18]=[C:17]1[CH2:16][CH2:15][CH2:14][C:11]1[CH:12]=[CH:13][C:8]([N:7]2[C:30](=[S:31])[N:29]([C:32]3[CH:39]=[CH:38][C:35]([C:36]#[N:37])=[C:34]([C:40]([F:41])([F:43])[F:42])[CH:33]=3)[C:1](=[O:46])[C:3]32[CH2:6][CH2:5][CH2:4]3)=[CH:9][CH:10]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 116155404-Isothiocyanato-2-(trifluoromethyl)benzonitrileHCID 86630011HCID 86630011, compound

Product 1

HCID 86630010HCID 86630010, compoundYield 52%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of tert-Butyl 2-(3-(4-(1-cyanocyclobutylamino)phenyl)propyl)-1H-imidazole-1-carboxylate (60) (22 mg, 0.06 mmol) and 4-isothiocyanato-2-trifluoromethylbenzonitrile (96) (26 mg, 0.12 mmol) in DMF (1 mL) was heated to 80° C. using microwave for 16 h. To this mixture was added methanol (3 mL) and aq. 1 N HCl (3 mL). The second mixture was refluxed for 1.5 h. After being cooled to room temperature, the reaction mixture was poured into cold water (30 mL), treated with saturated NaHCO3 solution and extracted with ethyl acetate (50 mL). The organic layer was dried over MgSO4, concentrated and the residue was purified with silica gel column chromatography (dichloromethane:acetone, 9:1) to give 4-(5-(4-(3-(1H-Imidazol-2-yl)propyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)-2-(trifluoromethyl)benzonitrile (59) [ND-12] (29 mg, 52%) as a pale yellowish solid: 1H NMR δ 8.65 (br s, 1H), 7.97 (d, 1H, J=2.0 Hz) 7.96 (d, 1H, J=8.4 Hz) 7.84 (dd, 1H, J=8.4, 2.0 Hz), 7.34 (d, 2H, J=8.2 Hz) 7.19 (d, 2H, J=8.2 Hz) 3.00 (t, 2H, J=7.5 Hz) 2.73 (t, 2H, J=7.7 Hz), 2.47-2.77 (m, 4H), 2.13-2.25 (m, 3H), 1.51-1.71 (m, 1H).

Workup

  1. customfor 16 h
  2. temperatureThe second mixture was refluxed for 1.5 h
  3. temperatureAfter being cooled to room temperature
  4. extractionextracted with ethyl acetate (50 mL)
  5. dry with materialThe organic layer was dried over MgSO4
  6. concentrationconcentrated
  7. customthe residue was purified with silica gel column chromatography (dichloromethane:acetone, 9:1)

Sources & evidence

ORD record
ord-e8102786d898450c91a31fdf019f2882
Source dataset
uspto-grants-2014_03
Patent number
US08680291B2

Reaction notes

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