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

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

Reactant 3

HCID 10340Sodium Carbonate

HCID 441195464-(Morpholin-4-ylsulphonyl)benzeneboronic acid

HCID 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).