Reaction #6980

Reaction equation

4-fluoro-3-{[2-(pyridin-2-ylamino)-thiazol-5-ylmethyl]-amino}-benzoic acid

compound 52A

4-fluoro-3-{[2-(pyridin-2-ylamino)-thiazol-5-ylmethyl]-amino}-benzoic acid

HATU

2,2-difluoro-1,3-propanediamine

DIPEA

→

title compound

Yield 65.0%

N-(3-Amino-2,2-difluoro-propyl)-4-fluoro-3-{[2-(pyridin-2-ylamino)-thiazol-5-ylmethyl]-amino}-benzamide

Yield 65.0%

Solvents

CH2Cl2

DMF

THF

Conditions

Workup

1. 1
   Washwashed with brine
2. 2
   Dryingdried over Na2SO4
3. 3
   Concentrationconcentrated
4. 4
   OtherThe residue was purified by flash column chromatography [silica gel, 5% (NH3/MeOH(2M) in EtOAc]

Procedure

To a mixture of 4-fluoro-3-{[2-(pyridin-2-ylamino)-thiazol-5-ylmethyl]-amino}-benzoic acid (compound 52A, 21 mg, 0.06 mmol) and HATU (38 mg, 0.1 mmol) in DMF (0.2 ml) and THF (0.4 ml), were added 2,2-difluoro-1,3-propanediamine (ref. Tetrahedron, 8617, 1994) (60 mg, 0.54 mmol) and DIPEA (26 mg, 0.2 mmol). The resulting mixture was stirred at RT for 18 h, then diluted with CH2Cl2, washed with brine, dried over Na2SO4 and concentrated. The residue was purified by flash column chromatography [silica gel, 5% (NH3/MeOH(2M) in EtOAc] to afford the title compound (17 mg, 65%) as a white solid. LC/MS; (M+H)+=437.

Source