反应 #41435

反应方程式

2,2-difluoropropanoic acid

HATU

DIPEA

2,2-difluoropropanoic acid

HATU

DIPEA

(1R,28)-1-(1-(4-chlorophenyl)-1H-indazol-5-yloxy)-1-(3-methoxyphenyl)propan-2-amine

(1R,2S)-1-(1-(4-chlorophenyl)-1H-indazol-5-yloxy)-1-(3-methoxyphenyl)propan-2-amine

→

crude product

N-((1R,2S)-1-(1-(4-chlorophenyl)-1H-indazol-5-yloxy)-1-(3-methoxyphenyl)propan-2-yl)-2,2-difluoropropanamide

溶剂

Water

NMP

NMP

NMP

反应条件

后处理

1. 1
   其他was stirrred at r.t. for another h
2. 2
   萃取the mixture was extracted with EtOAc (2×50 mL)
3. 3
   洗涤the organic phase was washed with 10% NaHSO4 (aq), brine
4. 4
   干燥dried over MgSO4
5. 5
   过滤filtered
6. 6
   其他evaporated

实验过程

(1R,28)-1-(1-(4-chlorophenyl)-1H-indazol-5-yloxy)-1-(3-methoxyphenyl)propan-2-amine (126a) (256 mg, 0.63 mmol) dissolved in NMP (3.5 mL) was added to a solution of 2,2-difluoropropanoic acid (111 mg, 1.00 mmol), HATU (382 mg, 1.00 mmol) and DIPEA (0.438 mL, 2.51 mmol) in NMP (1.5 mL). The reaction mixture was stirred at r.t. for 2 h. Additional 2,2-difluoropropanoic acid (80 mg, 0.73 mmol), HATU (278 mg, 0.73 mmol) and DIPEA (0.25 mL, 1.4 mmol) in NMP (1.5 mL) was added. The reaction mixture was stirrred at r.t. for another h. Water (50 mL) was added, the mixture was extracted with EtOAc (2×50 mL), the organic phase was washed with 10% NaHSO4 (aq), brine, dried over MgSO4, filtered and evaporated to give a crude product that was purified by HPLC. The fractions containing the product was combined and freeze dried. Yield 197 mg (62%).

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