Water → HCID 178470036, compound

HRID 1671338Notes

Reaction equation

HRID 1671338 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7](=[O:12])[NH:8][NH:9][C:10]=1[CH3:11])=[O:5])[CH3:2].C([O-])([O-])=O.[K+].[K+].Br[CH:20]([CH3:31])[C:21]([C:23]1[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][C:24]=1[CH3:30])=[O:22].O>CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1[C:7]([O:12][CH:20]([CH3:31])[C:21]([C:23]2[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][C:24]=2[CH3:30])=[O:22])=[N:8][NH:9][C:10]=1[CH3:11])=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 11389644HCID 11389644, compoundHCID 15725272HCID 15725272, compound

Product 1

HCID 178470036HCID 178470036, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a well stirred mixture of 5-methyl-3-oxo-2,3-dihydro-1H-pyrazole4-carboxylic acid ethyl ester (200 mg, 1.18 mmol, 1 eq.) and K2CO3 (179 mg, 1.29 mmol, 1.1 eq.) in DMF (5 ml) is added dropwise a solution of 2-bromo-1-(2,4-dimethyl-phenyl)-propan-1-one (Intermediate BA) (298 mg, 1.23 mmol, 1.05 eq.) in DMF (2.5 ml) at 50° C. After the addition, the reaction mixture is further stirred at 50° C. for 1 h then poured into water (50 ml) and extracted with EtOAc (2×25 ml). The combined organic fractions are dried over Na2SO4, filtered and concentrated to dryness under reduced pressure. The resulting crude residue is purified by Combi-Flash Companion™ (Isco Inc.) column chromatography (SiO2; gradient elution, [iso-hexane/DCM 1:1]/TBME 95:5→7:3) to yield the title compound as a white solid. TLC: RF=0.74 (iso-hexane/DCM/TBME 1:1:2); HPLC: AtRet=2.30; MS: m/z 331.3 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ 1.24 (t, J 7.1, 3H), 1.43 (d, J 6.8, 3H), 2.31 (s, 6H), 2.33 (s, 3H), 4.15 (m, 2H), 5.75 (q, J 6.8, 1H), 7.13 (m, 2H), 7.83 (m, 1H), 12.24 (br. s., 1H).

Workup

  1. additionAfter the addition
  2. stirringthe reaction mixture is further stirred at 50° C. for 1 h
  3. extractionextracted with EtOAc (2×25 ml)
  4. dry with materialThe combined organic fractions are dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated to dryness under reduced pressure
  7. customThe resulting crude residue is purified by Combi-Flash Companion™ (Isco Inc.) column chromatography (SiO2; gradient elution, [iso-hexane/DCM 1:1]/TBME 95:5→7:3)

Sources & evidence

ORD record
ord-458aeca7ad904f39a6c87503189d211c
Source dataset
uspto-grants-2011_08
Patent number
US07994203B2

Reaction notes

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