반응 #715620

반응 방정식

6-benzyl-4-chloro-1,7-dimethyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyridine

tert-butyl 4-aminopiperidine-1-carboxylate

NaOtBu

(9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine)

→

tert-butyl 4-[(6-benzyl-1,7-dimethyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyridin-4-yl)amino]piperidine-1-carboxylate

용매

EtOAc

toluene

반응 조건

후처리

1. 1
   온도Upon cooling
2. 2
   세척washed sequentially with water and brine
3. 3
   건조The organic layer was dried over sodium sulfate
4. 4
   여과filtered
5. 5
   농축concentrated
6. 6
   세척Flash chromatography, eluting with a gradient from 0-5% MeOH in DCM afforded product as a light yellow solid (0.15 g, 49%)
7. 7
   기타A portion (11 mg) of this solid was purified via preparative HPLC-MS (Waters XBridge C18
8. 8
   세척eluting with a gradient of MeCN/H2O containing 0.15% NH4OH)

실험 절차

A degassed mixture of 6-benzyl-4-chloro-1,7-dimethyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyridine (200. mg, 0.644 mmol, Example 228, Step 7), tert-butyl 4-aminopiperidine-1-carboxylate (520 mg, 2.6 mmol, Combi-Blocks), NaOtBu (180 mg, 1.9 mmol, Aldrich), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (93 mg, 0.16 mmol, Aldrich) and tris(dibenzylideneacetone)dipalladium(0) (71 mg, 0.077 mmol, Aldrich) in toluene (10. mL) was heated at 120° C. for 4 hours. Upon cooling, the reaction mixture was diluted with EtOAc and washed sequentially with water and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. Flash chromatography, eluting with a gradient from 0-5% MeOH in DCM afforded product as a light yellow solid (0.15 g, 49%). A portion (11 mg) of this solid was purified via preparative HPLC-MS (Waters XBridge C18, eluting with a gradient of MeCN/H2O containing 0.15% NH4OH). Yield: (7.1 mg, 65%).

출처