Sodium Carbonate → tert-butyl 4-(6-(6-(1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)-6-hydroxy-1,4-diazepane-1-carboxylate

HRID 57899Notes

Reaction equation

HRID 57899 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]2[CH:8]=[N:9][N:10]([C:11]3[N:16]=[C:15]([N:17]4[CH2:23][CH:22]([OH:24])[CH2:21][N:20]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:19][CH2:18]4)[CH:14]=[CH:13][CH:12]=3)[C:4]=2[CH:3]=1.CC1(C)C(C)(C)OB([C:40]2[CH:41]=[N:42][NH:43][CH:44]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH:42]1[CH:41]=[C:40]([C:2]2[N:7]=[CH:6][C:5]3[CH:8]=[N:9][N:10]([C:11]4[N:16]=[C:15]([N:17]5[CH2:23][CH:22]([OH:24])[CH2:21][N:20]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:19][CH2:18]5)[CH:14]=[CH:13][CH:12]=4)[C:4]=3[CH:3]=2)[CH:44]=[N:43]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 86707090tert-butyl 4-(6-(6-chloro-1H-pyrazolo[4,3-c]pyridin-1-yl)Pyridine-2-yl)-6-hydroxy-1,4-diazepane-1-carboxylate

Product 1

HCID 86707091tert-butyl 4-(6-(6-(1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)-6-hydroxy-1,4-diazepane-1-carboxylateYield 35%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of tert-butyl 4-(6-(6-chloro-1H-pyrazolo[4,3-c]pyridin-1-yl)Pyridine-2-yl)-6-hydroxy-1,4-diazepane-1-carboxylate (160 mg, 0.36 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (140 mg, 0.72 mmo), Pd(dppf)Cl2 (147 mg, 0.18 mmol), and aq. Na2CO3 (2.0 M, 1 mL) in 1,4-dioxane (10 mL) under nitrogen was heated at 100° C. for 16 hours. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography using EtOAc as eluting solvent to afford tert-butyl 4-(6-(6-(1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)-6-hydroxy-1,4-diazepane-1-carboxylate as a yellow solid (60 mg, 35%). MS (ESI) m/z: 477 [M+H]+.

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. customThe residue was purified by silica gel chromatography
  4. washas eluting solvent

Sources & evidence

ORD record
ord-ef9665f4ffe940e6a9cc0f11e3368b7e
Source dataset
uspto-grants-2016_09
Patent number
US09434725B2

Reaction notes

Loading…