Dimethyl Sulfoxide → HCID 71768545, compound

HRID 1746908Notes

Reaction equation

HRID 1746908 reaction equation
[NH2:1][C:2](=[O:40])[CH:3]([OH:39])[CH:4]([NH:12][C:13](=[O:38])[C:14]1[CH:19]=[CH:18][CH:17]=[N:16][C:15]=1[N:20]1[CH:24]=[CH:23][C:22]([CH2:25][N:26]2[CH2:31][CH2:30][CH:29]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH2:28][CH2:27]2)=[N:21]1)[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.CS(C)=O.ClC(Cl)C(O)=O>ClCCl>[NH2:1][C:2](=[O:40])[C:3](=[O:39])[CH:4]([NH:12][C:13](=[O:38])[C:14]1[CH:19]=[CH:18][CH:17]=[N:16][C:15]=1[N:20]1[CH:24]=[CH:23][C:22]([CH2:25][N:26]2[CH2:27][CH2:28][CH:29]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH2:30][CH2:31]2)=[N:21]1)[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1

Participants

5

Reactant 3

HCID 679Dimethyl SulfoxideHCID 6597Dichloroacetic AcidHCID 89854956HCID 89854956, compound

Product 1

HCID 71768545HCID 71768545, compoundYield 80.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of N-(4-amino-3-hydroxy-4-oxo-1-phenylbutan-2-yl)-2-(3-((4-phenylpiperidin-1-yl)methyl)-1H-pyrazol-1-yl)nicotinamide (100 mg, 0.186 mmol) in dichloromethane (3 mL) at room temperature DMSO (300 μL), N,N′-dichyclohexyl-carbodiimide (380 mg, 1.842 mmol) and 2,2-dichloroacetic acid (40 μL, 0.487 mmol) were added, and the mixture stirred for 1.5 h at room temperature. After completion of the reaction the mixture was filtered, the filtrate diluted with 30 mL of water, extracted with ethylacetate, the aqueous layer then adjusted to pH 8 by adding NaHCO3, then extracted again with ethyl acetate (3×30 mL), the combined organic layers washed with brine, dried (MgSO4), filtered and concentrated to give 80 mg of a yellow amorphous solid. Purification by chromatography over silica gel (CH2Cl2/methanol) and concentration afforded 25 mg of the title compound as white amorphous solid; ESI-MS [M+H]+: 537.2.

Workup

  1. customAfter completion of the reaction the mixture
  2. filtrationwas filtered
  3. additionthe filtrate diluted with 30 mL of water
  4. extractionextracted with ethylacetate
  5. additionby adding NaHCO3
  6. extractionextracted again with ethyl acetate (3×30 mL)
  7. washthe combined organic layers washed with brine
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-87cd6bd8689d449f817900f25fefd5f2
Source dataset
uspto-grants-2015_10
Patent number
US09150545B2

Reaction notes

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