Ethyl Acetate → HCID 178424525, compound

HRID 1508135Notes

Reaction equation

HRID 1508135 reaction equation
[CH3:1][C:2]1([CH3:28])[CH2:7][CH2:6][C:5]([C:8]2[CH:13]=[C:12]([C:14]([OH:17])([CH3:16])[CH3:15])[CH:11]=[CH:10][C:9]=2[NH:18][C:19]([C:21]2[NH:22][CH:23]=[C:24]([C:26]#[N:27])[N:25]=2)=[O:20])=[CH:4][CH2:3]1.C(Cl)(=O)C(Cl)=O.O[CH2:36][CH2:37][N:38]1[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1.CCOC(C)=O>C(Cl)Cl>[CH3:1][C:2]1([CH3:28])[CH2:7][CH2:6][C:5]([C:8]2[CH:13]=[C:12]([C:14]([CH3:15])([O:17][CH2:36][CH2:37][N:38]3[CH2:43][CH2:42][O:41][CH2:40][CH2:39]3)[CH3:16])[CH:11]=[CH:10][C:9]=2[NH:18][C:19]([C:21]2[NH:22][CH:23]=[C:24]([C:26]#[N:27])[N:25]=2)=[O:20])=[CH:4][CH2:3]1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 611632-MorpholinoethanolHCID 65578Oxalyl chlorideHCID 178424524HCID 178424524, compound

Product 1

HCID 178424525HCID 178424525, compoundYield 44.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 4-cyano-1H-imidazole-2-carboxylic acid [2-(4,4-dimethyl-cyclohex-1-enyl)-4-(1-hydroxy-1-methyl-ethyl)-phenyl]-amide (as prepared in Example 14, step (d), 50.0 mg, 0.132 mmol) in 1 mL of DCM at −15° C. was added oxalyl chloride (16 μL, 0.20 mmol) under Ar. After stirring at RT for 1 h, the mixture was cooled back to −15° C. To the reaction was added 2-hydroxylethylmorpholine (80 μL, 0.66 mmol) and the resulting mixture was warmed to RT and stirred for 16 h under Ar. Treated with EtOAc (30 mL), the mixture was washed with aqueous saturated NH4Cl (10 mL), H2O (10 mL) and brine (10 mL). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by silica gel chromatography (1-3% MeOH/DCM) to afford the title compound (29 mg, 44%) as a white solid. 1H-NMR (CDCl3; 400 MHz): δ 9.68 (s, 1H), 8.31 (d, 1H, J=8.6 Hz), 7.72 (s, 1H), 7.37 (dd, 1H, J=8.6, 2.3 Hz), 7.21 (d, 1H, J=2.3 Hz), 5.77 (m, 1H), 3.71 (t, 4H, J=4.7 Hz), 3.34 (t, 2H, J=6.2 Hz), 2.61 (t, 2H, J=6.2 Hz), 2.54 (m, 4H), 2.25-2.31 (m, 2H), 2.07-2.13 (m, 2H), 1.59 (t, 2H, J=6.3 Hz), 1.52 (s, 6H), 1.11 (s, 6H). Mass spectrum (ESI, m/z): Calcd. for C28H37N5O3, 492.3 (M+H). found 492.0.

Workup

  1. temperaturethe mixture was cooled back to −15° C
  2. temperaturethe resulting mixture was warmed to RT
  3. stirringstirred for 16 h under Ar
  4. washthe mixture was washed with aqueous saturated NH4Cl (10 mL), H2O (10 mL) and brine (10 mL)
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel chromatography (1-3% MeOH/DCM)

Sources & evidence

ORD record
ord-ef77220432314fc993d380e08e6455ad
Source dataset
uspto-grants-2015_12
Patent number
US09221797B2

Reaction notes

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