Potassium Acetate → 5-(5-(Cyclopropylcarbamoyl)-2-methylphenylcarbamoyl)thiophen-2-ylboronic acid

HRID 544946

Reaction equation

HRID 544946 reaction equation
ClC1C=CC=CC=1[C:8]1[CH:12]=[CH:11][S:10][C:9]=1[C:13]([NH:15][C:16]1[CH:21]=[C:20]([C:22](=[O:27])[NH:23][CH:24]2[CH2:26][CH2:25]2)[CH:19]=[CH:18][C:17]=1[CH3:28])=[O:14].[B:29]1(B2OC(C)(C)C(C)(C)O2)[O:33]C(C)(C)C(C)(C)[O:30]1.CC([O-])=O.[K+]>CN(C=O)C>[CH:24]1([NH:23][C:22]([C:20]2[CH:19]=[CH:18][C:17]([CH3:28])=[C:16]([NH:15][C:13]([C:9]3[S:10][C:11]([B:29]([OH:33])[OH:30])=[CH:12][CH:8]=3)=[O:14])[CH:21]=2)=[O:27])[CH2:26][CH2:25]1

Participants

5

Reactant 3

HCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 67148792(2-Chlorophenyl)-N-(5-(cyclopropylcarbamoyl)-2-methylphenyl)thiophene-2-carboxamide

Product 1

HCID 597615035-(5-(Cyclopropylcarbamoyl)-2-methylphenylcarbamoyl)thiophen-2-ylboronic acidYield 178.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 1.0 g (2.64 mmol) of 5-bromo-N-(5-(cyclopropylcarbamoyl)-2-methylphenyl)thiophene-2-carboxamide (Example 136, Step B), bis(pinacolato)diborane (1.0 g, 3.95 mmol) and KOAc (1.30 g, 13.2 mmol) in DMF (15 mL) was purged with argon and Pd(dppf)2Cl2/CH2Cl2 complex (65 mg, 0.08 mmol) was added followed by heating at 90° C. for 16 h. After cooling to rt, the mixture was partitioned between EtOAc (250 mL) and water (50 mL) and the layers were separated. The organic portion was washed with additional water, then brine, then dried over anhyd Na2SO4, filtered, and concentrated under vacuum to afford 1.62 g of a brown semi-solid as the crude product mixture. This material was triturated with EtOAc and filtered to afford 626 mg of the compound a containing ˜10% of the boronate ester. This material was used as is without any further purification. HPLC Ret time=2.36 min. LCMS [M+H]+ 345.2.

Workup

  1. additionwas added
  2. temperatureAfter cooling to rt
  3. customthe mixture was partitioned between EtOAc (250 mL) and water (50 mL)
  4. customthe layers were separated
  5. washThe organic portion was washed with additional water
  6. dry with materialbrine, then dried over anhyd Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-135ecc26917e4d76af946caa32bbb78a
Source dataset
uspto-grants-2011_05
Patent number
US07935696B2

Linked notes

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