Ethanol → (2-Chlorophenyl)-N-(5-(cyclopropylcarbamoyl)-2-methylphenyl)thiophene-2-carboxamide

HRID 544927Notes

Reaction equation

HRID 544927 reaction equation
Br[C:2]1[S:6][C:5]([C:7]([NH:9][C:10]2[CH:15]=[C:14]([C:16](=[O:21])[NH:17][CH:18]3[CH2:20][CH2:19]3)[CH:13]=[CH:12][C:11]=2[CH3:22])=[O:8])=[CH:4][CH:3]=1.[Cl:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1B(O)O.C(O)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[C:4]1[CH:3]=[CH:2][S:6][C:5]=1[C:7]([NH:9][C:10]1[CH:15]=[C:14]([C:16](=[O:21])[NH:17][CH:18]2[CH2:20][CH2:19]2)[CH:13]=[CH:12][C:11]=1[CH3:22])=[O:8]

Participants

8

Reactant 4

HCID 702EthanolHCID 62657Potassium Phosphate, TribasicHCID 27343222-Chlorophenylboronic acidHCID 597614015-Bromo-N-(5-(cyclopropylcarbamoyl)-2-methylphenyl)thiophene-2-carboxamide

Product 1

HCID 67148792(2-Chlorophenyl)-N-(5-(cyclopropylcarbamoyl)-2-methylphenyl)thiophene-2-carboxamideYield 64.9%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
115 °C

Procedure

5-Bromo-N-(5-(cyclopropylcarbamoyl)-2-methylphenyl)thiophene-2-carboxamide (80 mg, 0.21 mmol) and 2-chlorophenylboronic acid (50 mg, 0.32 mmol) in toluene (0.7 mL) was purged with argon and ethanol (0.14 mL), 2 M aq. K3PO4 (0.21 mL, 0.42 mmol), and Pd(PPh3)4 (12 mg, 0.010 mmol) was added. The resulting mixture was heated at 115° C. for 2 h. After cooling to rt, the mixture was diluted with EtOAc (100 mL), washed with brine and dried over anyhd. sodium sulfate. The solution was filtered and concentrated under vacuum to afford a yellow solid which was triturated with MeOH (2 mL), filtered to collect the solid and rinsed with additional MeOH (2×0.5 mL) and dried under vacuum to afford 56 mg of a white solid as the title compound (Example 136). HPLC Ret time=3.56 min. LCMS [M+H]+ 411.21.

Workup

  1. additionwas added
  2. temperatureAfter cooling to rt
  3. washwashed with brine
  4. customdried over anyhd
  5. filtrationThe solution was filtered
  6. concentrationconcentrated under vacuum
  7. customto afford a yellow solid which
  8. customwas triturated with MeOH (2 mL)
  9. filtrationfiltered
  10. customto collect the solid
  11. washrinsed with additional MeOH (2×0.5 mL)
  12. customdried under vacuum

Sources & evidence

ORD record
ord-853c6265e22d4ecba748bcb7a823bd8d
Source dataset
uspto-grants-2011_05
Patent number
US07935696B2

Reaction notes

Loading…