N,N'-Dimethylethylenediamine → tert-butyl 4-(6-(6-chloro-1H-pyrazolo[4,3-c]pyridin-1-yl)Pyridine-2-yl)-6-hydroxy-1,4-diazepane-1-carboxylate

HRID 57898Notes

Reaction equation

Br[C:2]1[N:7]=[C:6]([N:8]2[CH2:14][CH:13]([OH:15])[CH2:12][N:11]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:10][CH2:9]2)[CH:5]=[CH:4][CH:3]=1.[Cl:23][C:24]1[N:29]=[CH:28][C:27]2[CH:30]=[N:31][NH:32][C:26]=2[CH:25]=1.C([O-])([O-])=O.[K+].[K+].CNCCNC>O1CCOCC1.[Cu]I>[Cl:23][C:24]1[N:29]=[CH:28][C:27]2[CH:30]=[N:31][N:32]([C:2]3[N:7]=[C:6]([N:8]4[CH2:14][CH:13]([OH:15])[CH2:12][N:11]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:10][CH2:9]4)[CH:5]=[CH:4][CH:3]=3)[C:26]=2[CH:25]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a mixture of tert-butyl 4-(6-bromopyridin-2-yl)-6-hydroxy-1,4-diazepane-1-carboxylate (550 mg, 1.48 mmol) and 6-chloro-1H-pyrazolo[4,3-c]pyridine (207 mg, 1.34 mmol) in 1,4-dioxane (20 mL) was added CuI (102 mg, 0.54 mmol), K2CO3 (743 g, 5.4 mmol), and N1,N2-dimethylethane-1,2-diamine (95 mg, 1.08 mmol). The reaction mixture was heated at 100° C. for 3 hours, which was monitored by LCMS. After completion of the reaction, it was concentrated under reduced pressure. The crude was purified by silica gel chromatography using petroleum ether/EtOAc (2/1) as eluting solvents to afford tert-butyl 4-(6-(6-chloro-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)-6-hydroxy-1,4-diazepane-1-carboxylate as a light yellow solid (160 mg, 24.3%). MS (ESI) m/z: 445[M+H]+.

Workup

customAfter completion of the reaction, it
concentrationwas concentrated under reduced pressure
customThe crude was purified by silica gel chromatography
washas eluting solvents

Sources & evidence

ORD record: ord-49c0da34e1c746e88129f38927d61f98
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09434725B2

Reaction notes

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