Dimethyl Sulfoxide → HCID 89852695, compound

HRID 1746900Notes

Reaction equation

HRID 1746900 reaction equation
[NH2:1][C:2](=[O:34])[CH:3]([OH:33])[CH:4]([NH:12][C:13](=[O:32])[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][O:29][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.C([O-])(O)=O.[Na+]>[Cl-].[Na+].O>[NH2:1][C:2](=[O:34])[C:3](=[O:33])[CH:4]([NH:12][C:13](=[O:32])[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][O:29][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

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 6597Dichloroacetic AcidHCID 516892Sodium BicarbonateHCID 89852361HCID 89852361, compound

Product 1

HCID 89852695HCID 89852695, compoundYield 21.5%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of N-(4-amino-3-hydroxy-4-oxo-1-phenylbutan-2-yl)-2-(3-(morpholinomethyl)-1H-pyrazol-1-yl)nicotinamide (70 mg, 0.151 mmol) in DMSO (3 mL) EDC (240 mg, 1.252 mmol) and—after stirring for 5 min—2,2-dichloroacetic acid (50 μL, 0.609 mmol) were added, and the mixture stirred for 15 min at room temperature. 60 mL of a 1:1 mixture of brine and sat. NaHCO3-solution (60 mL) was added, the stirring continued for 10 min, extracted with ethylacetate (3×50 mL), the combined organic layers dried (MgSO4), filtered off and concentrated in vacuo to give 170 mg of the crude product as yellow oil. Treatment with 15 mL of methyl-tert.butylether (MTB) and further purification of the precipitate formed by chromatography over silica gel (CH2Cl2/methanol) afforded 15 mg of the title compound as amorphous white solid; ESI-MS [M+H]+: 463.2. 1H-NMR (400 MHz, DMSO), δ[ppm]: 8.95 (d, 1H), 8.51 (m, 1H), 8.30 (d, 1H), 8.05 (s, 1H), 7.82 (m, 1H), 7.70 (m, 1H), 7.44 (m, 1H), 7.30 (m, 5H), 6.38 (d, 1H), 5.38 (m, 1H), 3.53 (m, 4H), 3.15 and 2.88 (each dd, 1H), 2.29 (m, 4H).

Workup

  1. additionwere added
  2. additionwas added
  3. waitthe stirring continued for 10 min
  4. extractionextracted with ethylacetate (3×50 mL)
  5. dry with materialthe combined organic layers dried (MgSO4)
  6. filtrationfiltered off
  7. concentrationconcentrated in vacuo
  8. customto give 170 mg of the crude product as yellow oil
  9. customTreatment with 15 mL of methyl-tert.butylether (MTB) and further purification of the precipitate
  10. customformed by chromatography over silica gel (CH2Cl2/methanol)

Sources & evidence

ORD record
ord-68fc6243dc954747af633a5f355efa46
Source dataset
uspto-grants-2015_10
Patent number
US09150545B2

Reaction notes

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