Sodium Carbonate → Methyl 3-amino-6-bromo-2-(4-(morpholinosulfonyl)phenyl)isonicotinate

HRID 2410865Notes

Reaction equation

HRID 2410865 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([S:7]([C:10]2[CH:15]=[CH:14][C:13](B(O)O)=[CH:12][CH:11]=2)(=[O:9])=[O:8])[CH2:3][CH2:2]1.[NH2:19][C:20]1[C:29](Br)=[N:28][C:27]([Br:31])=[CH:26][C:21]=1[C:22]([O:24][CH3:25])=[O:23].C(=O)([O-])[O-].[Na+].[Na+]>>[NH2:19][C:20]1[C:29]([C:13]2[CH:14]=[CH:15][C:10]([S:7]([N:4]3[CH2:5][CH2:6][O:1][CH2:2][CH2:3]3)(=[O:9])=[O:8])=[CH:11][CH:12]=2)=[N:28][C:27]([Br:31])=[CH:26][C:21]=1[C:22]([O:24][CH3:25])=[O:23]

Participants

4

Reactant 3

HCID 10340Sodium CarbonateHCID 441195464-(Morpholin-4-ylsulphonyl)benzeneboronic acidHCID 53419616Methyl 3-amino-2,6-dibromoisonicotinate

Product 1

HCID 86663067Methyl 3-amino-6-bromo-2-(4-(morpholinosulfonyl)phenyl)isonicotinateYield 76%

Procedure

A flask containing mixture of 4-(morpholinosulfonyl)-phenylboronic acid (0.920 g, 3.39 mmol), methyl 3-amino-2,6-dibromoisonicotinate (0.877 g, 2.83 mmol), tetrakistriphenylphosphine palladium(0) (0.196 g, 0.170 mmol), sodium carbonate (0.719 g, 6.79 mmol) was flushed with nitrogen. Toluene (7 mL), and MeOH (2.4 mL) were added and the reaction was heated at reflux under nitrogen for 24 hr. The reaction was partitioned between EtOAc and water. The organic phase was washed with brine, dried with sodium sulfate, and the solvent removed. Radial silica gel chromatography (step gradient elution with DCM containing 0 to 20% EtOAc) afforded methyl 3-amino-6-bromo-2-(4-(morpholinosulfonyl)phenyl)isonicotinate (982 mg, 2.15 mmol, 76% yield) as a yellow solid. MS (ESI) m/z 457.9 (M+H). 1H NMR (500 MHz, chloroform-d) δ ppm 7.80-7.91 (5H, m), 5.94 (2H, br. s.), 3.94 (3H, s), 3.68-3.79 (4H, m), 2.98-3.07 (4H, m).

Workup

  1. additionA flask containing
  2. customwas flushed with nitrogen
  3. additionToluene (7 mL), and MeOH (2.4 mL) were added
  4. temperaturethe reaction was heated
  5. temperatureat reflux under nitrogen for 24 hr
  6. customThe reaction was partitioned between EtOAc and water
  7. washThe organic phase was washed with brine
  8. dry with materialdried with sodium sulfate
  9. customthe solvent removed
  10. washRadial silica gel chromatography (step gradient elution with DCM containing 0 to 20% EtOAc)

Sources & evidence

ORD record
ord-ce1ee12ffc114a08a19175026a6c2050
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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