Potassium Carbonate → 1h-Pyrazole-3-carboxamide,4-[3-(hydroxymethyl)phenyl]-1-[(4-methoxyphenyl)methyl]-n-phenyl-

HRID 2170591Notes

Reaction equation

HRID 2170591 reaction equation
[C:1]1([NH:7][C:8]([C:10]2[C:14](I)=[CH:13][N:12]([CH2:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=3)[N:11]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[K+].[K+].[OH:31][CH2:32][C:33]1[CH:34]=[C:35](B(O)O)[CH:36]=[CH:37][CH:38]=1>C(O)C.C1(C)C=CC=CC=1.O.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[C:1]1([NH:7][C:8]([C:10]2[C:14]([C:37]3[CH:36]=[CH:35][CH:34]=[C:33]([CH2:32][OH:31])[CH:38]=3)=[CH:13][N:12]([CH2:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=3)[N:11]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2734662[3-(Hydroxymethyl)phenyl]boronic acidHCID 668573141h-Pyrazole-3-carboxamide,4-iodo-1-[(4-methoxyphenyl)methyl]-n-phenyl-

Product 1

HCID 668554221h-Pyrazole-3-carboxamide,4-[3-(hydroxymethyl)phenyl]-1-[(4-methoxyphenyl)methyl]-n-phenyl-Yield 131.9%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 86587398Ethanol toluene waterSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 4-iodo-1-(4-methoxy-benzyl)-1H-pyrazole-3-carboxylic acid phenylamide (50 mg; 0.11 mmol), bis(tri-tert-butylphosphine)palladium (12 mg), potassium carbonate (100 mg; 0.66 mmol) and 3-(hydroxymethyl)benzene boronic acid (21 mg; 0.14 mmol) in ethanol/toluene/water (4 ml:1 ml:1 ml) was heated at 120° C. (50 W) for 15 minutes in a CEM Discover microwave synthesiser. The reaction was evaporated and the residue partitioned between ethyl acetate and brine. The ethyl acetate layer was separated, dried (MgSO4), filtered and evaporated and the crude material purified by flash column chromatography eluting with 1:2 then 2:1 ethyl acetate/hexane. Product containing fractions were combined and evaporated to give 60 mg of 4-(3-hydroxymethyl-phenyl)-1-(4-methoxy-benzyl)-1H-pyrazole-3-carboxylic acid phenylamide.

Workup

  1. customThe reaction was evaporated
  2. customthe residue partitioned between ethyl acetate and brine
  3. customThe ethyl acetate layer was separated
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customthe crude material purified by flash column chromatography
  8. washeluting with 1:2
  9. additionProduct containing fractions
  10. customevaporated

Sources & evidence

ORD record
ord-dcf639fa86be438888c4a0ea51aa6ae2
Source dataset
uspto-grants-2015_06
Patent number
US09051278B2

Reaction notes

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