Ethyl Acetate → HCID 178424517, compound

HRID 1190112Notes

Reaction equation

HRID 1190112 reaction equation
[CH3:1][C:2]1([CH3:28])[CH2:7][CH2:6][C:5]([C:8]2[CH:13]=[C:12]([C:14](O)([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.O=S(Cl)Cl.[NH:33]1[CH2:38][CH2:37][S:36][CH2:35][CH2:34]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]([CH3:16])([N:33]3[CH2:38][CH2:37][S:36][CH2:35][CH2:34]3)[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

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 24386Thionyl ChlorideHCID 67164ThiomorpholineHCID 178424524HCID 178424524, compound

Product 1

HCID 178424517HCID 178424517, compoundYield 88%

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 the previous step, 65 mg, 0.17 mmol) in 1.5 mL of DCM at 0° C. was added SOCl2 (38 μL, 0.52 mmol) under Ar. After stirring at RT for 1 h, the mixture was cooled back to 0° C. To the reaction was added thiomorpholine (172 μL, 1.72 mmol) and the resulting mixture was stirred at 0° C. for 1 h. After warming to RT, the mixture was treated with EtOAc (30 mL) and washed with H2O (2×10 mL) and brine (10 mL). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by silica gel chromatography (5% EtOAc/DCM then 1-2% MeOH/DCM) to afford the title compound (70 mg, 88%) as a white solid. 1H-NMR (CDCl3; 400 MHz): δ 11.90 (s, 1H), 9.65 (s, 1H), 8.28 (d, 1H, J=8.6 Hz), 7.74 (s, 1H), 7.45 (dd, 1H, J=8.6, 2.3 Hz), 7.33 (d, 1H, J=2.3 Hz), 5.78 (m, 1H), 2.77 (m, 4H), 2.65 (m, 4H), 2.29 (m, 2H), 2.12 (m, 2H), 1.60 (t, 2H, J=6.3 Hz), 1.33 (s, 6H), 1.12 (s, 6H). Mass spectrum (ESI-neg, m/z): Calcd. for C26H33N5OS, 462.2 (M−H). found 462.4.

Workup

  1. temperaturethe mixture was cooled back to 0° C
  2. stirringthe resulting mixture was stirred at 0° C. for 1 h
  3. temperatureAfter warming to RT
  4. washwashed with H2O (2×10 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 (5% EtOAc/DCM

Sources & evidence

ORD record
ord-1d124b19e188411889bdeac4658223ee
Source dataset
uspto-grants-2014_03
Patent number
US08674100B2

Reaction notes

Loading…