반응 #41457

반응 방정식

dimethylamine

2,2,2-trifluoro-N-((1R,2S)-1-(1-(4-(hydroxymethyl)phenyl)-1H-indazol-5-yloxy)-1-phenylpropan-2-yl)acetamide

triethylamine

methanesulfonyl chloride

→

title compound

N-((1R,2S)-1-(1-(4-((dimethylamino)methyl)phenyl)-1H-indazol-5-yloxy)-1-phenylpropan-2-yl)-2,2,2-trifluoroacetamide

용매

brine

dichloromethane

반응 조건

후처리

1. 1
   온도To a stirred, ice-cooled
2. 2
   workup.ADDITIONwere added
3. 3
   세척The mixture was washed with aqueous KHSO4 (1M) and sat. aqueous NaHCO3
4. 4
   기타was then evaporated

실험 절차

To a stirred, ice-cooled suspension of 2,2,2-trifluoro-N-((1R,2S)-1-(1-(4-(hydroxymethyl)phenyl)-1H-indazol-5-yloxy)-1-phenylpropan-2-yl)acetamide (141, 118 mg, 0.25 mmol) and triethylamine (0.35 mL, 2.5 mmol) was added methanesulfonyl chloride (140 μL, 1.8 mmol). After stirring for 50 min at 0° C. brine and dichloromethane (10 mL) were added. The mixture was washed with aqueous KHSO4 (1M) and sat. aqueous NaHCO3. To the organic phase was added dimethylamine (0.75 mL, 11.3 mmol). The mixture was stirred at ambient temperature for 40 min and was then evaporated. Preparative HPLC (Kromasil C-18, 2.5×20 cm, 30-90% CH3CN in water/40 min (0.1% TfA) afforded slightly impure title compound as a TfA-salt. The material was dissolved in MeOH and absorbed on a plug of acidic ion exchange resin (SCX, 5 g, pre-washed with MeOH). Eluting subsequently with MeOH and methanolic ammonia (2M) gave somewhat impure title compound. Purification by preparative HPLC on an XBridge C-18 column using a gradient of 50-90% acetonitrile in water containing 0.1% aqueous ammonia (28%). afforded pure N-((1R,2S)-1-(1-(4-((dimethylamino)methyl)phenyl)-1H-indazol-5-yloxy)-1-phenylpropan-2-yl)-2,2,2-trifluoroacetamide (77 mg, 61%).

출처