Sodium bis(trimethylsilyl)amide → (R)-4-((R)-1-((6-(1-(tert-butyl)-1H-pyrazol-4-yl)-2-methylpyrazolo[1,5-a]pyridin-4-yl)oxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

HRID 2209262Notes

Reaction equation

HRID 2209262 reaction equation
[C:1]([N:5]1[CH:9]=[C:8]([C:10]2[CH:11]=[C:12]([OH:20])[C:13]3[N:14]([N:16]=[C:17]([CH3:19])[CH:18]=3)[CH:15]=2)[CH:7]=[N:6]1)([CH3:4])([CH3:3])[CH3:2].CS(O[C@H:26]([C@@H:28]1[CH2:32][C:31](=[O:33])[N:30]([C@@H:34]([C:36]2[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=2)[CH3:35])[CH2:29]1)[CH3:27])(=O)=O.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>CN(C=O)C.C1COCC1>[C:1]([N:5]1[CH:9]=[C:8]([C:10]2[CH:11]=[C:12]([O:20][C@@H:26]([C@H:28]3[CH2:29][N:30]([C@@H:34]([C:36]4[CH:37]=[CH:38][C:39]([O:42][CH3:43])=[CH:40][CH:41]=4)[CH3:35])[C:31](=[O:33])[CH2:32]3)[CH3:27])[C:13]3[N:14]([N:16]=[C:17]([CH3:19])[CH:18]=3)[CH:15]=2)[CH:7]=[N:6]1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 117842947(S)-1-((R)-1-((R)-1-(4-methoxyphenyl)ethyl)-5-oxopyrrolidin-3-yl)ethyl methanesulfonateHCID 1178433566-(1-(tert-butyl)-1H-pyrazol-4-yl)-2-methylpyrazolo[1,5-a]pyridin-4-ol

Product 1

HCID 117843934(R)-4-((R)-1-((6-(1-(tert-butyl)-1H-pyrazol-4-yl)-2-methylpyrazolo[1,5-a]pyridin-4-yl)oxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-oneYield 31.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-(1-(tert-butyl)-1H-pyrazol-4-yl)-2-methylpyrazolo[1,5-a]pyridin-4-ol (5 mg) in DMF (3 mL) was added (S)-1-((R)-5-oxo-1-((R)-1-phenylethyl)pyrrolidin-3-yl)ethyl methanesulfonate 1.30 (9 mg) and 1 M solution of NaHMDS in THF (0.15 mL) at rt. After 2 h. the reaction mixture was extracted with ethyl acetate. Combined organics were washed with brine, dried, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to provide to provide 3 mg of (R)-4-((R)-1-((6-(1-(tert-butyl)-1H-pyrazol-4-yl)-2-methylpyrazolo[1,5-a]pyridin-4-yl)oxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one. LCMS [M+H]+: 517.18.

Workup

  1. extractionAfter 2 h. the reaction mixture was extracted with ethyl acetate
  2. washCombined organics were washed with brine
  3. customdried
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography
  7. customto provide

Sources & evidence

ORD record
ord-95a07301c920408ea46011c810552654
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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