Triethylamine → (S)-tert-butyl 3-((7-chloro-3-cyanoisoquinolin-1-yl)amino)pyrrolidine-1-carboxylate

HRID 1476892Notes

Reaction equation

Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([Cl:12])[CH:10]=2)[CH:5]=[C:4]([C:13]#[N:14])[N:3]=1.[NH2:15][C@H:16]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17]1.CCN(CC)CC>CN1C(=O)CCC1>[Cl:12][C:9]1[CH:10]=[C:11]2[C:6]([CH:5]=[C:4]([C:13]#[N:14])[N:3]=[C:2]2[NH:15][C@H:16]2[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17]2)=[CH:7][CH:8]=1

Participants

Conditions

Temperature: 160 °C

Procedure

To a solution of 1,7-dichloroisoquinoline-3-carbonitrile (500 mg, 2.24 mmol) in NMP (5 mL) was added (S)-tert-butyl 3-aminopyrrolidine-1-carboxylate (460 mg, 2.46 mmol) and Et3N (453 mg, 4.48 mmol). The solution was heated to 160° C. for 30 minutes in a microwave reactor. The reaction was quenched with H2O (20 mL) and extracted with EtOAc (3×10 mL). The organic layers were combined and concentrated in vacuo. The crude product was purified by column chromatography eluting with ethyl acetate and petroleum ether (EtOAc/PE=1:10 to 1:5 gradient) to give the title compound (660 mg, 79%). ESI-MS m/z [M+H-tert-butyl]+ 317.

Workup

customThe reaction was quenched with H2O (20 mL)
extractionextracted with EtOAc (3×10 mL)
concentrationconcentrated in vacuo
customThe crude product was purified by column chromatography
washeluting with ethyl acetate and petroleum ether (EtOAc/PE=1:10 to 1:5 gradient)

Sources & evidence

ORD record: ord-e9e52bcb4d5d4d8cb8e3ce8de20c3c18
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09402841B2

Reaction notes

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