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

HRID 57890Notes

Reaction equation

HRID 57890 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][CH2:22][CH2:21][N:20]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:19][CH2:18]4)[CH:14]=[N:13][CH:12]=3)[C:4]=2[CH:3]=1.CC1(C)C(C)(C)OB([C:39]2[CH:40]=[N:41][NH:42][CH:43]=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:41]1[CH:40]=[C:39]([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][CH2:22][CH2:21][N:20]([C:24]([O:26][C:27]([CH3:28])([CH3:29])[CH3:30])=[O:25])[CH2:19][CH2:18]5)[CH:14]=[N:13][CH:12]=4)[C:4]=3[CH:3]=2)[CH:43]=[N:42]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 86707066Tert-butyl 4-[6-(6-chloropyrazolo[4,3-c]pyridin-1-yl)pyrazin-2-yl]-1,4-diazepane-1-carboxylate

Product 1

HCID 86707082tert-butyl 4-(6-(6-(1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyrazin-2-yl)-1,4-diazepane-1-carboxylateYield 42%

Reagents, catalysts & solvents 2

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

Procedure

A suspension of tert-butyl 4-(6-(6-chloro-1H-pyrazolo[4,3-c]pyridin-1-yl)pyrazin-2-yl)-1,4-diazepane-1-carboxylate (400 mg, 0.93 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (271 mg, 1.4 mmol), Pd(dppf)Cl2 (81 mg, 0.093 mmol) and a solution of Na2CO3 (2.0 M, 1.5 mL) in 1,4-dioxane (6 mL) under argon in a sealed vial was heated at 120° C. for 1 hour. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel chromatography using petroleum ether/ethyl acetate (10% to 60%) as eluting solvents to afford tert-butyl 4-(6-(6-(1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyrazin-2-yl)-1,4-diazepane-1-carboxylate as yellow solid (180 mg, 42%). MS (ESI) m/z: 462 [M+H]+.

Workup

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

Sources & evidence

ORD record
ord-f84e3271cae24df98515130a57a0ff24
Source dataset
uspto-grants-2016_09
Patent number
US09434725B2

Reaction notes

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