Ammonium formate → 6-(4-oxo-2-phenoxymethyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-5-yl)-3',4',5',6'-tetrahydro-2'H-[2,4']bipyridinyl-1'-carboxylic acid tert-butyl ester

HRID 2046228Notes

Reaction equation

HRID 2046228 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([N:20]3[CH2:25][CH2:24][N:23]4[N:26]=[C:27]([CH2:29][O:30][C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=5)[CH:28]=[C:22]4[C:21]3=[O:37])[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])=O.[NH4+]>[Pd].CO>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([N:20]3[CH2:25][CH2:24][N:23]4[N:26]=[C:27]([CH2:29][O:30][C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=5)[CH:28]=[C:22]4[C:21]3=[O:37])[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 574100246-(4-oxo-2-phenoxymethyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-5-yl)-3',6'-dihydro-2'H-[2,4']bipyridinyl-1'-carboxylic acid tert-butyl ester

Product 1

HCID 679916106-(4-oxo-2-phenoxymethyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-5-yl)-3',4',5',6'-tetrahydro-2'H-[2,4']bipyridinyl-1'-carboxylic acid tert-butyl esterYield 87.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
80 °C

Procedure

10% Palladium on charcoal (11 mg, 0.01 mmol) was added to a stirred suspension of 6-(4-oxo-2-phenoxymethyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-5-yl)-3′,6′-dihydro-2′H-[2,4′]bipyridinyl-1′-carboxylic acid tert-butyl ester (51 mg, 0.10 mmol) and ammonium formate (38 mg, 0.61 mmol) in MeOH (0.5 mL) in a sealed tube and under nitrogen. The mixture was stirred at 80° C. for 30 minutes. The mixture was filtered through a pad of diatomaceous earth and washed with DCM. The filtrate was treated with brine and extracted with more DCM. The organic layer was separated, dried (MgSO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 50/50). The desired fractions were collected and the solvents evaporated in vacuo to yield 6-(4-oxo-2-phenoxymethyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-5-yl)-3′,4′,5′,6′-tetrahydro-2′H-[2,4′]bipyridinyl-1′-carboxylic acid tert-butyl ester (44 mg, 86% yield) as a yellow oil.

Workup

  1. filtrationThe mixture was filtered through a pad of diatomaceous earth
  2. washwashed with DCM
  3. additionThe filtrate was treated with brine
  4. extractionextracted with more DCM
  5. customThe organic layer was separated
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customthe solvents evaporated in vacuo
  9. customThe crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 50/50)
  10. customThe desired fractions were collected
  11. customthe solvents evaporated in vacuo

Sources & evidence

ORD record
ord-2de923f6c0884faca72e4c5b2e520222
Source dataset
uspto-grants-2013_11
Patent number
US08592422B2

Reaction notes

Loading…