Dimethylformamide → 5-[2-{[(Tert-butoxycarbonyl)amino]methyl}-4-(dimethylamino)phenyl]thiophene-2-carboxylic acid

HRID 1712940Notes

Reaction equation

HRID 1712940 reaction equation
Br[C:2]1[CH:16]=[CH:15][C:14](OC)=[CH:13][C:3]=1[CH2:4][NH:5][C:6](=[O:12])[O:7][C:8]([CH3:11])([CH3:10])[CH3:9].OB(O)[C:21]1[S:25][C:24]([C:26]([OH:28])=[O:27])=[CH:23][CH:22]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:36][N:37](C=O)[CH3:38]>O>[C:8]([O:7][C:6]([NH:5][CH2:4][C:3]1[CH:13]=[C:14]([N:37]([CH3:38])[CH3:36])[CH:15]=[CH:16][C:2]=1[C:21]1[S:25][C:24]([C:26]([OH:28])=[O:27])=[CH:23][CH:22]=1)=[O:12])([CH3:9])([CH3:10])[CH3:11]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 27798075-Boronothiophene-2-carboxylic acidHCID 22930485Tert-butyl (2-bromo-5-methoxybenzyl)carbamate

Product 1

HCID 594632795-[2-{[(Tert-butoxycarbonyl)amino]methyl}-4-(dimethylamino)phenyl]thiophene-2-carboxylic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A solution of tert tert-butyl (2-bromo-5-methoxybenzyl)carbamate (0.226 g, 0.69 mmol), 5-(dihydroxyboryl)thiophene-2-carboxylic acid (0.118 g, 0.69 mmol) and cesium carbonate (0.492 g, 1.51 mmol) in DMF (2 mL) and water (1 mL) was degassed. To this solution was added PdCl2dppf (1:1 complex with DCM, 0.020 g, 0.03 mmol). The reaction mixture was heated at 100° C. for 36 hr and then allowed to cool to rt and concentrated. The residue was suspended in acetonitrile (15 mL) and MeOH (2 mL) containing 0.1% TFA and adsorbed onto celite and purified by reverse phase chromatography to give a mixture of the desired product and remaining starting material. This mixture was suspended in half-saturated sodium bicarbonate solution (10 mL) and washed with EtOAc (20 mL). The organic solution was extracted with half-saturated sodium bicarbonate solution until no product was apparent in the organic solution. The pH of the aqueous solution was adjusted to 5 with 1N HCl and then was extracted with EtOAc. The organic solutions were combined, washed with brine, dried over Na2SO4, filtered and concentrated to give 5-[2-{[(tert-butoxycarbonyl)amino]methyl}-4-(dimethylamino)phenyl]thiophene-2-carboxylic acid (0.036 g, 13%) as a yellow oil. LCMS: (AA) ES+ 377.2, ES-375.3.

Workup

  1. temperatureto cool to rt
  2. concentrationconcentrated
  3. additionMeOH (2 mL) containing 0.1% TFA
  4. custompurified by reverse phase chromatography
  5. customto give

Sources & evidence

ORD record
ord-8f4cd63f2f3d443db88b22d7ce111858
Source dataset
uspto-grants-2010_09
Patent number
US07795249B2

Reaction notes

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