Ethyl Acetate → HCID 86658565, compound

HRID 1520214Notes

Reaction equation

HRID 1520214 reaction equation
I[C:2]1[C:6]([C:7]([N:9]([O:11][CH3:12])[CH3:10])=[O:8])=[CH:5][N:4]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)[N:3]=1.[F:22][C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1.C(N(C(C)C)C(C)C)C.CCOC(C)=O>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:22][C:23]1[CH:28]=[CH:27][C:26]([C:2]2[C:6]([C:7]([N:9]([O:11][CH3:12])[CH3:10])=[O:8])=[CH:5][N:4]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[N:3]=2)=[CH:25][CH:24]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 2856454-Fluorophenylboronic acidHCID 86658566HCID 86658566, compound

Product 1

HCID 86658565HCID 86658565, compoundYield 90.8%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
180 °C

Procedure

According to Scheme 11 Step 1: A solution of 3-iodo-N-methoxy-1-(4-methoxybenzyl)-N-methyl-1H-pyrazole-4-carboxamide (2.49 mmol, 1.00 g), 4-fluorophenylboronic acid (2.99 mmol, 419 mg), Pd(dppf)Cl2 (0.25 mmol, 204 mg) and N-ethyl-N-isopropylpropan-2-amine (4.99 mmol, 850 μL) in a mixture of dioxane/water (5 mL, 1:1) was heated at 180° C. for 50 minutes under microwave heating and a nitrogen atmosphere. AcOEt was added and the organic phase was washed with a saturated aqueous solution of Na2CO3. The organic layer was dried over MgSO4, was filtered and was concentrated. The crude compound was purified by flash chromatography with silica gel using cyclohexane/AcOEt (100:0 to 50:50) to yield 3-(4-fluorophenyl)-N-methoxy-1-(4-methoxybenzyl)-N-methyl-1H-pyrazole-4-carboxamide (2.26 mmol, 833 mg, 90%).

Workup

  1. temperatureheating
  2. washthe organic phase was washed with a saturated aqueous solution of Na2CO3
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationwas filtered
  5. concentrationwas concentrated
  6. customThe crude compound was purified by flash chromatography with silica gel

Sources & evidence

ORD record
ord-7f53244c43b942cdbed8917e6c2a48ec
Source dataset
uspto-grants-2015_07
Patent number
US09073907B2

Reaction notes

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