Ammonium Chloride → HCID 178424478, compound

HRID 536926Notes

Reaction equation

HRID 536926 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[NH:12][CH:13]=[C:14]([C:16]#[N:17])[N:15]=2)=[O:10])=[C:4]([C:18]2[CH2:23][CH2:22][C:21]([CH3:25])([CH3:24])[CH2:20][CH:19]=2)[CH:3]=1.C([Mg]Cl)(C)C.C([Li])(C)(C)C.[S:36]1[CH2:41][CH2:40][C:39](=[O:42])[CH2:38][CH2:37]1.[NH4+].[Cl-]>C1COCC1.CCOC(C)=O>[CH3:24][C:21]1([CH3:25])[CH2:22][CH2:23][C:18]([C:4]2[CH:3]=[C:2]([C:39]3([OH:42])[CH2:40][CH2:41][S:36][CH2:37][CH2:38]3)[CH:7]=[CH:6][C:5]=2[NH:8][C:9]([C:11]2[NH:12][CH:13]=[C:14]([C:16]#[N:17])[N:15]=2)=[O:10])=[CH:19][CH2:20]1

Participants

8

Reactant 5

HCID 25517Ammonium ChlorideHCID 66173Tetrahydrothiopyran-4-oneHCID 178418306HCID 178418306, compoundHCID 178418918HCID 178418918, compoundHCID 1784244434-Cyano-1H-imidazole-2-carboxylic acid [4-bromo-2-(4,4-dimethyl-cyclohex-1-enyl)-phenyl]-amide

Product 1

HCID 178424478HCID 178424478, compoundYield 65%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-cyano-1H-imidazole-2-carboxylic acid [4-bromo-2-(4,4-dimethyl-cyclohex-1-enyl)-phenyl]-amide (as prepared in Example 1, step (g), 120 mg, 0.300 mmol) in 4 mL of THF at −78° C. under Ar was added isopropylmagnesium chloride (165 μL, 0.331 mmol, 2.0 M in THF). The resulting mixture was warmed to RT and stirred for 5 min, cooled to −78° C. again. To the mixture was added tert-butyllithium (530 μL, 0.902 mmol, 1.7 M in pentane) and the resulting mixture was stirred at −78° C. for 10 min. A solution of tetrahydro-thiopyran-4-one (175 mg, 1.50 mmol) in 1 mL of THF was then added, and the reaction was warmed to RT and stirred for 0.5 h under Ar. The mixture was treated with 2 mL of saturated NH4Cl followed by 20 mL of EtOAc, washed with brine (10 mL) and dried (Na2SO4). Removal of the solvent under reduced pressure followed by flash chromatography of the residue on silica gel (1-2% MeOH/DCM) gave 85.0 mg (65%) of the title compound as a white solid. 1H-NMR (CDCl3; 400 MHz): δ 12.62 (s, 1H), 9.72 (s, 1H), 8.32 (d, 1H, J=8.6 Hz), 7.74 (d, 1H, J=2.3 Hz), 7.42 (dd, 1H, J=8.6, 2.3 Hz), 7.33 (d, 1H, J=2.3 Hz), 5.78 (m, 1H), 3.12-3.33 (br s, 2H), 2.46-2.54 (m, 2H), 2.26-2.33 (m, 2H), 2.16-2.22 (m, 2H), 2.00-2.13 (m, 4H), 1.79 (s, 1H), 1.59 (t, 2H, J=6.3 Hz), 1.10 (s, 6H). Mass spectrum (ESI, m/z): Calcd. for C24H28N4O2S, 437.2 (M+H). found 437.2.

Workup

  1. temperaturecooled to −78° C. again
  2. stirringthe resulting mixture was stirred at −78° C. for 10 min
  3. temperaturethe reaction was warmed to RT
  4. stirringstirred for 0.5 h under Ar
  5. washwashed with brine (10 mL)
  6. dry with materialdried (Na2SO4)
  7. customRemoval of the solvent under reduced pressure

Sources & evidence

ORD record
ord-f059db7e2cd143438d66f0f122705447
Source dataset
uspto-grants-2014_10
Patent number
US08859602B2

Reaction notes

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