Potassium Carbonate → HCID 136009496, compound

HRID 1969670Notes

Reaction equation

HRID 1969670 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@@H:5]([CH2:20][C:21](OCC)=[O:22])[CH2:4]1)[CH3:2].O/[N:27]=[C:28](\[NH2:31])/[CH2:29][OH:30].C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.CO>[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]2[O:22][N:31]=[C:28]([CH2:29][OH:30])[N:27]=2)[CH2:4]1)[CH3:2]

Participants

6

Reactant 3

HCID 11430Potassium Carbonate2×HCID 4049105773728-45-73×HCID 136009208HCID 136009208, compound

Product 1

HCID 136009496HCID 136009496, compoundYield 20%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of 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 (0.195 g, 0.571 mmol, Example #38, Step H) in toluene (1.00 mL) and MeOH (1.000 mL) were added (Z)-N′,2-dihydroxyacetimidamide (0.515 g, 5.71 mmol, Tyger) and K2CO3 (0.195 g, 1.41 mmol). The reaction was heated in a CEM microwave at about 130° C. twice at about 45 min each (250 psi maximum pressure, 1 min ramp, 300 max watts). (Z)-N′,2-dihydroxy acetimidamide (0.200 g, 2.22 mmol, Tyger) was added and the reaction mixture was heated in a CEM microwave at about 140° C. for about 45 min (250 psi maximum pressure, 1 min ramp, 300 max watts). (Z)-N′,2-dihydroxyacetimidamide (0.200 g, 2.22 mmol, Tyger) and K2CO3 (0.100 g, 0.725 mmol) were added, and the reaction mixture was heated in a CEM microwave at about 140° C. for about 45 min (250 psi maximum pressure, 1 min ramp, 300 max watts). The solvent was removed under reduced pressure. The residue was dissolved with water (20 mL) and EtOAc (50 mL). The aqueous layer was extracted with EtOAc (5×50 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concd to give a yellow residue. The crude material was purified via flash chromatography on silica gel eluting with a gradient of 0-10% MeOH in EtOAc to afford (5-(((1S,3R,4S)-3-ethyl-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)methyl)-1,2,4-oxadiazol-3-yl)methanol (0.042 g, 20%) as a yellow solid: LC/MS (Table 1, Method a) Rt=1.67 min; MS m/z: 368 (M+H)+.

Workup

  1. temperaturethe reaction mixture was heated in a CEM microwave at about 140° C. for about 45 min (250 psi maximum pressure, 1 min ramp, 300 max watts)
  2. temperaturethe reaction mixture was heated in a CEM microwave at about 140° C. for about 45 min (250 psi maximum pressure, 1 min ramp, 300 max watts)
  3. customThe solvent was removed under reduced pressure
  4. dissolutionThe residue was dissolved with water (20 mL) and EtOAc (50 mL)
  5. extractionThe aqueous layer was extracted with EtOAc (5×50 mL)
  6. dry with materialThe combined organic layers were dried over anhydrous MgSO4
  7. filtrationfiltered
  8. customconcd to give a yellow residue
  9. customThe crude material was purified via flash chromatography on silica gel eluting with a gradient of 0-10% MeOH in EtOAc

Sources & evidence

ORD record
ord-8bcca509d2654a5a95d2092667343eb7
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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