Water → HCID 178457705, compound

HRID 624117Notes

Reaction equation

HRID 624117 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][N:6]([C:11]([NH:13][C:14]1[CH:19]=[CH:18][C:17]([C:20](=[O:25])[NH:21][CH2:22][CH2:23][CH3:24])=[CH:16][CH:15]=1)=[O:12])[CH2:5]2.[NH:26]1[CH:30]=[CH:29][C:28](B(O)O)=[N:27]1.C(=O)(O)[O-].[Na+].O>CN(C)C=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:22]([NH:21][C:20]([C:17]1[CH:18]=[CH:19][C:14]([NH:13][C:11]([N:6]2[CH2:5][C:4]3[C:8](=[CH:9][CH:10]=[C:2]([C:30]4[CH:29]=[CH:28][NH:27][N:26]=4)[CH:3]=3)[CH2:7]2)=[O:12])=[CH:15][CH:16]=1)=[O:25])[CH2:23][CH3:24]

Participants

7

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 57509908HCID 57509908, compoundHCID 178514837HCID 178514837, compound

Product 1

HCID 178457705HCID 178457705, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

In a 4 mL vial, a solution of 5-bromo-N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxamide (50 mg, 0.12 mmol) and 1H-pyrazol-3-ylboronic acid (17 mg, 0.15 mmol) in dimethylformamide was treated with saturated aqueous sodium bicarbonate followed by bis(triphenylphosphine)palladium(II) chloride (7 mg). The vial was capped under nitrogen and the reaction heated at 85° C. for 6 hours. The reaction was cooled to ambient temperature and water was added. The resulting suspension was stirred for 5 minutes and filtered. The solid collected was washed with water and dried under vacuum; the solid was purified by reverse-phase HPLC to provide the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 12.39-13.18 (bs, 1H), 8.59 (s, 1H), 8.24-8.28 (m, 1H), 7.75-7.79 (m, 2H), 7.70-7.80 (m, 3H), 7.62-7.69 (m, 2H), 7.40 (d, J=7.9 Hz, 1H), 6.73 (d, J=2.2 Hz, 1H), 4.79-4.83 (m, 4H), 3.15-3.25 (m, 2H), 1.46-1.57 (m, 2H), 0.89 (t, J=7.4 Hz, 3H); MS (ESI(+)) m/e 390 (M+H)+.

Workup

  1. customThe vial was capped under nitrogen
  2. temperatureThe reaction was cooled to ambient temperature
  3. filtrationfiltered
  4. customThe solid collected
  5. washwas washed with water
  6. customdried under vacuum
  7. customthe solid was purified by reverse-phase HPLC

Sources & evidence

ORD record
ord-cabdc3d5c2434740a6dd7a4ca9b2be9f
Source dataset
uspto-grants-2016_04
Patent number
US09302989B2

Reaction notes

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