6-chloro-4-((R)-1-((R)-1-((R)-1-(4-methoxyphenyl)ethyl)-5-oxopyrrolidin-3-yl)ethoxy)pyrazolo[1,5-a]pyrazine-3-carbonitrile → 6-chloro-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)pyrazolo[1,5-a]pyrazine-3-carbonitrile

HRID 2209226Notes

Reaction equation

[Cl:1][C:2]1[N:3]=[C:4]([O:13][C@@H:14]([C@@H:16]2[CH2:20][C:19](=[O:21])[N:18]([C@@H](C3C=CC(OC)=CC=3)C)[CH2:17]2)[CH3:15])[C:5]2[N:6]([N:8]=[CH:9][C:10]=2[C:11]#[N:12])[CH:7]=1>C(O)(C(F)(F)F)=O>[Cl:1][C:2]1[N:3]=[C:4]([O:13][C@@H:14]([C@@H:16]2[CH2:20][C:19](=[O:21])[NH:18][CH2:17]2)[CH3:15])[C:5]2[N:6]([N:8]=[CH:9][C:10]=2[C:11]#[N:12])[CH:7]=1

Participants

Conditions

Temperature: 70 °C

Procedure

Intermediate 5.64 (41 mg, 0.093 mmol) was dissolved in TFA (1.5 mL) and the resulting solution was heated to 70° C. After stirring 6.5 h, the reaction mixture was cooled and concentrated in vacuo. The resulting residue was partitioned between EtOAc, water, and brine. The phases were separated, and the aqueous phase was extracted with EtOAc. The combined organic phase was dried over Na2SO4, filtered, and concentrated to afford crude 6-chloro-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)pyrazolo[1,5-a]pyrazine-3-carbonitrile (5.65) that was used without further purification. LCMS-ESI+ (m/z): [M+H]+ calcd for C13H13ClN5O2: 306.1; found: 305.8.

Workup

temperaturethe reaction mixture was cooled
concentrationconcentrated in vacuo
customThe resulting residue was partitioned between EtOAc, water, and brine
customThe phases were separated
extractionthe aqueous phase was extracted with EtOAc
dry with materialThe combined organic phase was dried over Na2SO4
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-f6105274284b4ef3ac54f498d32a6cea
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09376441B2

Reaction notes

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