HCID 136009271, compound → HCID 136009214, compound

HRID 1969614Notes

Reaction equation

HRID 1969614 reaction equation
[CH2:1]([C@H:3]1[C@@H:7]([C:8]2[N:12]3[C:13]4[CH:19]=[CH:18][NH:17][C:14]=4[N:15]=[CH:16][C:11]3=[N:10][N:9]=2)[CH2:6]/[C:5](=[CH:20]/[C:21]([O:23][CH2:24][CH3:25])=[O:22])/[CH2:4]1)[CH3:2]>C1COCC1.[OH-].[OH-].[Pd+2]>[CH2:1]([C@H:3]1[C@@H:7]([C:8]2[N:12]3[C:13]4[CH:19]=[CH:18][NH:17][C:14]=4[N:15]=[CH:16][C:11]3=[N:10][N:9]=2)[CH2:6][C@H:5]([CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:4]1)[CH3:2]

Participants

4

Reactant 1

HCID 136009271HCID 136009271, compound

Product 1

HCID 136009214HCID 136009214, compoundYield 31%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a slurry of 20 wt % Pd(OH)2 on carbon (0.134 g, 0.192 mmol) in THF (20 mL) was added a solution of (E)-ethyl 2-((cis)-3-ethyl-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentylidene)acetate (1.3 g, 3.83 mmol, Example #38, Step G) in THF (5 mL). The reaction mixture was sparged with hydrogen and an atmosphere of hydrogen was maintained via balloon. After about 3 days, the reaction mixture was filtered through Celite®, concd under reduced pressure and purified by flash chromatography on silica gel eluting with EtOAc to afford a dark brown/black solid. The compound was further by purified by chiral chromatography (Table 2, Method 47) to afford ethyl 2-((1R,3R,4S)-3-ethyl-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)acetate [W.1.1](Rt=12.0 min, or =negative) (0.400 g, 31%): LC/MS (Table 1, Method a) Rt=1.85 min; MS m/z: 342 (M+H)+ and ethyl 2-((1S,3R,4S)-3-ethyl-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)acetate [W.1.2](Rt=13.7 min, or =negative) (0.420 g, 32%) as a white solid: LC/MS (Table 1, Method a) Rt=1.85 min; MS m/z: 342 (M+H)+.

Workup

  1. customThe reaction mixture was sparged with hydrogen
  2. temperaturean atmosphere of hydrogen was maintained via balloon
  3. filtrationthe reaction mixture was filtered through Celite®, concd under reduced pressure
  4. custompurified by flash chromatography on silica gel eluting with EtOAc
  5. customto afford a dark brown/black solid
  6. customby purified by chiral chromatography (Table 2, Method 47)

Sources & evidence

ORD record
ord-69da4d06bf174fbab635777371e64c74
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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