Dimethyl Sulfoxide → HCID 88868832, compound

HRID 1626827Notes

Reaction equation

HRID 1626827 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH2:11]([O:13][C:14](=[O:55])[CH2:15][NH:16][C:17]([C:19]1[C:24]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[C:23]([CH3:33])[N:22]=[C:21]([CH2:34][CH:35]2[CH2:40][CH2:39][N:38]([C:41]3[CH:46]=[CH:45][C:44]([C:47]4[CH:52]=[CH:51][C:50]([CH2:53][OH:54])=[CH:49][CH:48]=4)=[CH:43][CH:42]=3)[CH2:37][CH2:36]2)[N:20]=1)=[O:18])[CH3:12].C(N(CC)CC)C>ClCCl.O>[CH2:11]([O:13][C:14](=[O:55])[CH2:15][NH:16][C:17]([C:19]1[C:24]([O:25][CH2:26][C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)=[C:23]([CH3:33])[N:22]=[C:21]([CH2:34][CH:35]2[CH2:40][CH2:39][N:38]([C:41]3[CH:42]=[CH:43][C:44]([C:47]4[CH:48]=[CH:49][C:50]([CH:53]=[O:54])=[CH:51][CH:52]=4)=[CH:45][CH:46]=3)[CH2:37][CH2:36]2)[N:20]=1)=[O:18])[CH3:12]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 68196361HCID 68196361, compound

Product 1

HCID 88868832HCID 88868832, compoundYield 87.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Procedure

Oxalyl chloride (0.31 g, 2.5 mmol) was dissolved in dichloromethane (5 mL), and a solution of dimethyl sulfoxide (0.18 g, 2.3 mmol) in dichloromethane (4 mL) was added dropwise at −78° C., followed by stirring at the same temperature for 15 minutes. To the reaction solution was added dropwise a solution of ethyl({[5-(benzyloxy)-2-{(1-[4′-(hydroxymethyl)biphenyl-4-yl]piperidin-4-yl}methyl)-6-methylpyrimidin-4-yl]carbonyl}amino)acetate (1.0 g, 1.6 mmol) obtained in Example 1-(11) in dichloromethane (26 mL), followed by stirring at the same temperature for 25 minutes, and subsequently triethylamine (1.1 mL, 8.2 mmol) was added dropwise, and the temperature was raised to room temperature over 1.5 hours. Water was added to the reaction solution, followed by extraction with dichloromethane, and subsequently the extract was washed with a saturated aqueous sodium chloride solution, and dried over anhydrous sodium sulfate. After the solvent was distilled off under reduced pressure, the resulting residue was purified by chromatography on a silica gel column (Biotage Ltd., elution solvent: dichloromethane/ethyl acetate) to afford the title compound (0.85 g, 1.4 mmol) as a yellow solid (yield 85%).

Workup

  1. stirringby stirring at the same temperature for 25 minutes
  2. extractionfollowed by extraction with dichloromethane
  3. washsubsequently the extract was washed with a saturated aqueous sodium chloride solution
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationAfter the solvent was distilled off under reduced pressure
  6. customthe resulting residue was purified by chromatography on a silica gel column (Biotage Ltd., elution solvent: dichloromethane/ethyl acetate)

Sources & evidence

ORD record
ord-0a922e49d28f4592aed6e2b9a22577de
Source dataset
uspto-grants-2014_07
Patent number
US08785462B2

Reaction notes

Loading…