Triethylamine → HCID 90387035, compound

HRID 1476886Notes

Reaction equation

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

Participants

Conditions

Temperature: 160 °C

Procedure

To a solution of 1,3-dichloro-7-fluoroisoquinoline (1 g, 4.6 mmol) in NMP (15 mL) was added (S)-tert-butyl 3-aminopyrrolidine-1-carboxylate (1.72 g, 9.3 mmol) and Et3N (1.4 g, 14 mmol). The reaction mixture was heated at 160° C. for 2 hours. The mixture was subsequently partition between H2O (20 mL) and EtOAc (20 mL). The aqueous phase was extracted with EtOAc (3×20 mL). The organic layers were combined, dried over Na2SO4, and concentrated. The crude product was purified by column chromatography eluting with petroleum ether and ethyl acetate (PE/EA=10:1-5:1 gradient) to give the title compound (1.2 g, 70%). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.26-8.23 (d, J=10.8 Hz, 1H), 7.82-7.80 (dd, J1=8.8 Hz, J2=5.2 Hz, 1H), 7.68-7.67 (d, J=5.6 Hz 1H), 7.63-7.60 (t, J=8.8 Hz, 1H), 7.10 (s, 1H), 4.63-4.53 (m, 1H), 3.70-3.66 (m, 1H), 3.48-3.45 (m, 1H), 3.29-3.26 (m, 1H), 2.23-2.18 (m, 1H), 2.03-1.97 (m, 1H), 1.40 (s, 9H).

Workup

customThe mixture was subsequently partition between H2O (20 mL) and EtOAc (20 mL)
extractionThe aqueous phase was extracted with EtOAc (3×20 mL)
dry with materialdried over Na2SO4
concentrationconcentrated
customThe crude product was purified by column chromatography
washeluting with petroleum ether and ethyl acetate (PE/EA=10:1-5:1 gradient)

Sources & evidence

ORD record: ord-3368a7a392bf4809a09121a30b3d5e93
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09402841B2

Reaction notes

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