Dimethyl Sulfoxide → HCID 66749619, compound

HRID 2401818Notes

Reaction equation

HRID 2401818 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([CH:18]([OH:47])[C:19]2[CH:20]=[C:21]([C:37]3[CH:42]=[CH:41][N:40]=[C:39]([NH:43][C:44](=[O:46])[CH3:45])[CH:38]=3)[S:22][C:23]=2[C:24]2[N:28]=[CH:27][N:26]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[N:25]=2)=[CH:14][CH:13]=1.C(N(CC)CC)C>C(Cl)Cl>[Cl:11][C:12]1[CH:13]=[CH:14][C:15]([C:18]([C:19]2[CH:20]=[C:21]([C:37]3[CH:42]=[CH:41][N:40]=[C:39]([NH:43][C:44](=[O:46])[CH3:45])[CH:38]=3)[S:22][C:23]=2[C:24]2[N:28]=[CH:27][N:26]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:34])([CH3:35])[CH3:36])[N:25]=2)=[O:47])=[CH:16][CH:17]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 66748152HCID 66748152, compound

Product 1

HCID 66749619HCID 66749619, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent4×

Procedure

A solution of oxalyl chloride (63.1 uL, 0.746 mmol) in methylene chloride (1.50 mL, 23.4 mmol) was cooled to −78° C. To this solution was added dimethyl sulfoxide (65.1 uL, 0.918 mmol) in methylene chloride (1.00 mL) dropwise. The reaction was stirred for 10 min under an atmosphere of Nitrogen. To this mixture was added a solution of N-{4-[4-[(4-chlorophenyl)(hydroxy)methyl]-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-2-thienyl]pyridin-2-yl}acetamide (319 mg, 0.574 mmol) in methylene chloride (1.50 mL) dropwise. In 1 hr, triethylamine (0.400 mL, 2.87 mmol) was added dropwise to the reaction and the resulting mixture was warmed to rt. In 1 hr, the solution was diluted with CH2Cl2 and washed with water. The aqueous layer was extracted with CH2Cl2(×2). The combined org layer was washed with NaHCO3(aq) saturated solution, dried, and concentrated to provide N-{4-[4-(4-chlorobenzoyl)-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-2-thienyl]pyridin-2-yl}acetamide as a yellow solid (325 mg, quantative). LCMS: (AA) 554, 556; 1H NMR (400 MHz, CDCl3) δ 8.56-8.47 (s, 1H), 8.32-8.24 (m, 1H), 8.11-8.03 (s, 1H), 8.03-7.92 (s, 1H), 7.87-7.77 (m, 2H), 7.63-7.57 (s, 1H), 7.42-7.32 (m, 3H), 5.37-5.32 (s, 2H), 3.53-3.40 (t, J=8.1 Hz, 2H), 2.27-2.19 (s, 3H), 0.94-0.80 (t, J=8.1 Hz, 2H), 0.02-−0.04 (s, 9H).

Workup

  1. waitIn 1 hr
  2. waitIn 1 hr
  3. washwashed with water
  4. extractionThe aqueous layer was extracted with CH2Cl2(×2)
  5. washThe combined org layer was washed with NaHCO3(aq) saturated solution
  6. customdried
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-952c5f5b182e4cf1933e83ebb2754552
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

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