Diisopropylamine → (R)-ethyl 5-(2-(2-(3-(tert-butoxycarbonylamino)prop-1-ynyl)-5-fluoropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate

HRID 1426967Notes

Reaction equation

Cl[C:2]1[C:7]([C@H:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C:13]2[CH:18]=[CH:17][N:16]3[N:19]=[CH:20][C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[C:15]3[N:14]=2)=[CH:6][C:5]([F:27])=[CH:4][N:3]=1.[CH2:28]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[C:29]#[CH:30].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(NC(C)C)(C)C>CN(C=O)C.[Cu]I>[C:34]([O:33][C:32]([NH:31][CH2:28][C:29]#[C:30][C:2]1[C:7]([C@H:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C:13]2[CH:18]=[CH:17][N:16]3[N:19]=[CH:20][C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[C:15]3[N:14]=2)=[CH:6][C:5]([F:27])=[CH:4][N:3]=1)=[O:38])([CH3:37])([CH3:36])[CH3:35]

Participants

Conditions

Temperature: 95 °C

Procedure

(R)-ethyl 5-(2-(2-chloro-5-fluoropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate (Example 12, Step C; 153 mg, 0.392 mmol) in DMF (2 mL) was added tert-butyl prop-2-ynylcarbamate (122 mg, 0.785 mmol), copper(I) iodide (11 mg, 0.0578 mmol), triphenylphosphine (82.4 mg, 0.314 mmol), di-triphenylphosphine palladium(II) chloride (116 mg, 0.165 mmol), and diisopropylamine (99.3 mg, 0.981 mmol). The reaction mixture was sealed and heated to 95° C. for 8 hours, then cooled to ambient temperature and concentrated under reduced pressure The residue was purified by silica column chromatography, eluting with 33% EtOAc/Hexanes to afford the final product mixed with Ph3P (160 mg, 80.2% yield). MS (apci) m/z=508.9 (M+H).

Workup

customThe reaction mixture was sealed
temperaturecooled to ambient temperature
concentrationconcentrated under reduced pressure The residue
customwas purified by silica column chromatography
washeluting with 33% EtOAc/Hexanes

Sources & evidence

ORD record: ord-26487476a1274f9c92d62eb10e7bac36
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08933084B2

Reaction notes

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