Sodium hydride → (S)-tert-butyl 3-((6-bromo-1,7-naphthyridin-8-yl)amino)pyrrolidine-1-carboxylate

HRID 1476858Notes

Reaction equation

[NH2:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1.[H-].[Na+].[Br:16][C:17]1[CH:18]=[C:19]2[C:24](=[C:25](Br)[N:26]=1)[N:23]=[CH:22][CH:21]=[CH:20]2>CN1CCCC1=O.O>[Br:16][C:17]1[CH:18]=[C:19]2[C:24](=[C:25]([NH:1][C@H:2]3[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]3)[N:26]=1)[N:23]=[CH:22][CH:21]=[CH:20]2

Participants

Conditions

Temperature: 135 °C

Procedure

To (S)-tert-butyl 3-aminopyrrolidine-1-carboxylate (0.776 g, 4.17 mmol) in N-methyl-2-pyrrolidinone (12 mL) at 0° C. was added NaH (0.139 g, 3.47 mmol). The mixture was stirred for 5 minutes. Next, 6,8-dibromo-1,7-naphthyridine (1 g, 3.47 mmol) was added and the reaction mixture was stirred at RT for 5 minutes and then heated at 135° C. for 30 minutes in a microwave reactor. The reaction mixture was diluted with water and extracted with EtOAc (2×). The organic layers were combined, dried over Na2SO4, and concentrated. The crude product was purified using silica column chromatography eluting with a gradient of 0-75% EtOAc in hexane over a 45 minute period to give the title compound as a yellow solid (1.3 g, 95%).

Workup

stirringthe reaction mixture was stirred at RT for 5 minutes
extractionextracted with EtOAc (2×)
dry with materialdried over Na2SO4
concentrationconcentrated
customThe crude product was purified
washeluting with a gradient of 0-75% EtOAc in hexane over a 45 minute period

Sources & evidence

ORD record: ord-0c5f25d02ce449cda1f7196e53bac91e
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09402841B2

Reaction notes

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