반응 #715593

반응 방정식

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

tert-butyl (3R)-3-aminopyrrolidine-1-carboxylate

sodium tert-butoxide

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

→

title compound

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

용매

toluene

반응 조건

후처리

1. 1
   기타The reaction mixture was partitioned between water and ethyl acetate
2. 2
   추출the aqueous layer was extracted further with two portions of EtOAc
3. 3
   세척The combined organic extracts were washed with brine
4. 4
   건조dried over sodium sulfate
5. 5
   기타decanted
6. 6
   농축concentrated
7. 7
   기타The product was purified by flash chromatography
8. 8
   세척eluting first with a gradient from 0-100% EtOAc in hexanes
9. 9
   세척eluting with 5% MeOH in DCM
10. 10
    기타A portion of this material was then purified by preparative HPLC-MS (Waters XBridge C18
11. 11
    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 (200.0 mg, 0.6435 mmol, Example 228, Step 7), tert-butyl (3R)-3-aminopyrrolidine-1-carboxylate (0.40 mL, 2.3 mmol, Aldrich), sodium tert-butoxide (190 mg, 1.98 mmol, Aldrich), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (93 mg, 0.16 mmol, Aldrich) and tris(dibenzylideneacetone)dipalladium(0) (74 mg, 0.080 mmol, Aldrich) in toluene (12 mL) was heated at 100° C. for 3.5 hours, then at 125° C. for 2 hours. The reaction mixture was partitioned between water and ethyl acetate, and the aqueous layer was extracted further with two portions of EtOAc. The combined organic extracts were washed with brine, dried over sodium sulfate, decanted and concentrated. The product was purified by flash chromatography, eluting first with a gradient from 0-100% EtOAc in hexanes, then eluting with 5% MeOH in DCM. Yield: (190 mg, 64%). A portion of this material was then purified by preparative HPLC-MS (Waters XBridge C18, eluting with a gradient of MeCN/H2O containing 0.15% NH4OH) to provide a pure title compound.

출처