تفاعل #6980

معادلة التفاعل

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

المردود 65.0%

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

المردود 65.0%

المذيبات

CH2Cl2

DMF

THF

ظروف التفاعل

المعالجة

1. 1
   غسيلwashed with brine
2. 2
   تجفيفdried over Na2SO4
3. 3
   تركيزconcentrated
4. 4
   أخرىThe residue was purified by flash column chromatography [silica gel, 5% (NH3/MeOH(2M) in EtOAc]

الإجراء التجريبي

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.

المصدر