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

HRID 2209225Notes

Reaction equation

[Cl:1][C:2]1[N:3]=[C:4]([OH:13])[C:5]2[N:6]([N:8]=[CH:9][C:10]=2[C:11]#[N:12])[CH:7]=1.O[C@H:15]([C@H:17]1[CH2:21][N:20]([C@@H:22]([C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)[CH3:23])[C:19](=[O:32])[CH2:18]1)[CH3:16].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[Cl:1][C:2]1[N:3]=[C:4]([O:13][C@@H:15]([C@@H:17]2[CH2:18][C:19](=[O:32])[N:20]([C@@H:22]([C:24]3[CH:25]=[CH:26][C:27]([O:30][CH3:31])=[CH:28][CH:29]=3)[CH3:23])[CH2:21]2)[CH3:16])[C:5]2[N:6]([N:8]=[CH:9][C:10]=2[C:11]#[N:12])[CH:7]=1

Participants

Conditions

Temperature: 45 °C

Procedure

6-chloro-4-hydroxypyrazolo[1,5-a]pyrazine-3-carbonitrile (122 mg, 0.627 mmol) was dissolved in THF (1 mL). (R)-4-((8)-1-hydroxyethyl)-1-4R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 1.05 (255 mg, 0.97 mmol) and PPh3 (255 mg, 0.97 mmol) were added followed by diethyl azodicarboxylate (0.16 mL, 1.0 mmol). The resulting mixture was heated to 45° C. and was stirred for 45 min. The mixture was then cooled to r.t., let stand overnight, and concentrated onto 2 g silica gel. Purification by silica gel chromatography (25-100% EtOAc in hexanes) provided 6-chloro-4-((R)-1-((R)-1-((R)-1-(4-methoxyphenyl)ethyl)-5-oxopyrrolidin-3-yl)ethoxy)pyrazolo[1,5-a]pyrazine-3-carbonitrile (5.64). LCMS-ESI+ (m/z): [M+H]+ calcd for C22H23ClN5O3: 440.1; found: 439.8.

Workup

temperatureThe mixture was then cooled to r.t.
waitlet stand overnight
concentrationconcentrated onto 2 g silica gel
customPurification by silica gel chromatography (25-100% EtOAc in hexanes)

Sources & evidence

ORD record: ord-484c7ae137934f288d18bbb5191757e4
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09376441B2

Reaction notes

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