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

HRID 57981Notes

Reaction equation

HRID 57981 reaction equation
[F:1][C:2]([F:19])([F:18])[CH2:3][N:4]1[CH:8]=[C:7]([C:9]2[N:14]=[CH:13][C:12]3[CH:15]=[N:16][NH:17][C:11]=3[CH:10]=2)[CH:6]=[N:5]1.[Br:20][C:21]1[C:22]([N:28]2[CH2:34][CH:33]([OH:35])[CH2:32][N:31]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:30][CH2:29]2)=[N:23][C:24](I)=[CH:25][CH:26]=1.CNCCNC.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.[Cu]I>[Br:20][C:21]1[C:22]([N:28]2[CH2:34][CH:33]([OH:35])[CH2:32][N:31]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:30][CH2:29]2)=[N:23][C:24]([N:17]2[C:11]3[CH:10]=[C:9]([C:7]4[CH:6]=[N:5][N:4]([CH2:3][C:2]([F:1])([F:18])[F:19])[CH:8]=4)[N:14]=[CH:13][C:12]=3[CH:15]=[N:16]2)=[CH:25][CH:26]=1

Participants

7

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 11430Potassium CarbonateHCID 86707160Tert-butyl 4-(3-bromo-6-iodopyridin-2-yl)-6-hydroxy-1,4-diazepane-1-carboxylateHCID 867071626-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridine

Product 1

HCID 86707164tert-butyl 4-(3-bromo-6-(6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)-6-hydroxy-1,4-diazepane-1-carboxylateYield 19%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridine (539 mg, 2.02 mmol), tert-butyl 4-(3-bromo-6-iodopyridin-2-yl)-6-hydroxy-1,4-diazepane-1-carboxylate (1.00 g, 2.02 mmol), N1,N2-dimethylethane-1,2-diamine (535 mg, 6.06 mmol), CuI (768 mg, 4.04 mmol), and K2CO3 (1.12 g, 8.08 mmol) in 1,4-dioxane (10 mL) under N2 was heated at 100° C. for 20 hours. The reaction mixture was concentrated under reduced pressure. The residue was purified by silica gel chromatography using EtOAc/petroleum Ether (20%40%) as eluting solvents to afford tert-butyl 4-(3-bromo-6-(6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)-6-hydroxy-1,4-diazepane-1-carboxylate as a white solid (244 mg, 19%). MS (ESI) m/z: 637 [M+H]+.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customThe residue was purified by silica gel chromatography
  3. washas eluting solvents

Sources & evidence

ORD record
ord-8872937cf7b04785b6becb72d8ac13a3
Source dataset
uspto-grants-2016_09
Patent number
US09434725B2

Reaction notes

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