Triethylamine → HCID 178428031, compound

HRID 2067695Notes

Reaction equation

HRID 2067695 reaction equation
C(Cl)(=O)C(Cl)=O.[CH2:7]([CH:14]1[CH2:18][NH:17][C:16]([C:19]2[S:23][C:22]([N:24]3[CH2:28][CH2:27][N:26]([CH2:29][C:30]4[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=4)[C:25]3=[O:37])=[CH:21][C:20]=2[CH3:38])=[N:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C(N(CC)CC)C>ClCCl>[CH2:7]([C:14]1[N:15]=[C:16]([C:19]2[S:23][C:22]([N:24]3[CH2:28][CH2:27][N:26]([CH2:29][C:30]4[CH:31]=[CH:32][C:33]([F:36])=[CH:34][CH:35]=4)[C:25]3=[O:37])=[CH:21][C:20]=2[CH3:38])[NH:17][CH:18]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 178428030HCID 178428030, compound

Product 1

HCID 178428031HCID 178428031, compoundYield 9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of oxalyl chloride (0.05 mL, 0.62 mmol) in dichloromethane (1 mL) at −78° C. under nitrogen atmosphere was added dropwise N,N-dimethylsulfoxide (0.06 mL, 0.83 mmol). After 10 minutes, 1-(5-(4-benzyl-4,5-dihydro-1H-imidazol-2-yl)-4-methylthiophen-2-yl)-3-(4-fluorobenzyl)imidazolidin-2-one (0.06 g, 0.14 mmol) in dichloromethane (0.5 mL) was added dropwise. The resulting mixture was stirred at −78° C. for 40 minutes, then triethylamine (0.23 mL, 1.66 mmol) was added, and the cooling bath was removed. After stirred for 1 h, the reaction mixture was partitioned between water (25 mL) and dichloromethane (50 mL). The aqueous layer was extracted with dichloromethane (50 mL), and the combined organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by ion exchange chromatography eluted sequentially with methanol, 2.0 M ammonia in methanol solution, and further purified by preparative thin layer chromatography eluted with dichloromethane/methanol/triethylamine (95/5/0.5) to afford the title compound as a light yellow solid in 9% yield (0.01 g): 1H NMR (300 MHz, CDCl3) δ 7.34-7.21 (m, 8H), 7.06-6.99 (m, 2H), 6.72 (s, 1H), 6.13 (s, 1H), 4.41 (s, 2H), 3.98 (s, 2H), 3.81-3.73 (m, 2H), 3.44-3.37 (m, 2H), 2.42 (s, 3H); MS (ES+) m/z 447.2 (M+1).

Workup

  1. customthe cooling bath was removed
  2. stirringAfter stirred for 1 h
  3. customthe reaction mixture was partitioned between water (25 mL) and dichloromethane (50 mL)
  4. extractionThe aqueous layer was extracted with dichloromethane (50 mL)
  5. dry with materialthe combined organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by ion exchange chromatography
  9. washeluted sequentially with methanol, 2.0 M ammonia in methanol solution
  10. customfurther purified by preparative thin layer chromatography
  11. washeluted with dichloromethane/methanol/triethylamine (95/5/0.5)

Sources & evidence

ORD record
ord-de86f545d3e344489a6a8e2900247b1f
Source dataset
uspto-grants-2012_10
Patent number
US08293768B2

Reaction notes

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