Cesium carbonate → tert-butyl (+/-)-6-hydroxy-4-(3-methyl-6-(6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)-1,4-diazepane-1-carboxylate

HRID 57982Notes

Reaction equation

HRID 57982 reaction equation
Br[C:2]1[C:3]([N:27]2[CH2:33][CH:32]([OH:34])[CH2:31][N:30]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:29][CH2:28]2)=[N:4][C:5]([N:8]2[C:16]3[CH:15]=[C:14]([C:17]4[CH:18]=[N:19][N:20]([CH2:22][C:23]([F:26])([F:25])[F:24])[CH:21]=4)[N:13]=[CH:12][C:11]=3[CH:10]=[N:9]2)=[CH:6][CH:7]=1.[CH3:42]B1OB(C)OB(C)O1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[OH:34][CH:32]1[CH2:31][N:30]([C:35]([O:37][C:38]([CH3:39])([CH3:41])[CH3:40])=[O:36])[CH2:29][CH2:28][N:27]([C:3]2[C:2]([CH3:42])=[CH:7][CH:6]=[C:5]([N:8]3[C:16]4[CH:15]=[C:14]([C:17]5[CH:18]=[N:19][N:20]([CH2:22][C:23]([F:25])([F:24])[F:26])[CH:21]=5)[N:13]=[CH:12][C:11]=4[CH:10]=[N:9]3)[N:4]=2)[CH2:33]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 75806TricyclohexylphosphineHCID 574072TrimethylboroxineHCID 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-carboxylate

Product 1

HCID 86707165tert-butyl (+/-)-6-hydroxy-4-(3-methyl-6-(6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)-1,4-diazepane-1-carboxylateYield 55.2%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 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 (244 mg, 0.38 mmol), 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane (194 mg, 1.53 mmol), Pd2 dba3 (174 mg, 0.19 mmol), Pcy3 (107 mg, 0.38 mmol), and Cs2CO3 (500 mg, 1.53 mmol) in 1,4-dioxane (10 mL) was heated in a microwave oven at 110° C. for 1.5 hour. The reaction mixture was concentrated under reduced pressure. The residue was purified by silica gel chromatography using EtOAc/petroleum Ether (20%˜80%) as eluting solvents to afford tert-butyl(±)-6-hydroxy-4-(3-methyl-6-(6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)-1,4-diazepane-1-carboxylate as a white solid (120 mg, 55%). MS (ESI) m/z: 573 [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-c6df478e47ad4130b642ee7b508b220c
Source dataset
uspto-grants-2016_09
Patent number
US09434725B2

Reaction notes

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