Toluene → tert-butyl methyl(1-(4-(1-methyl-1H-pyrazol-5-yl)phthalazin-1-yl)piperidin-4-yl)carbamate

HRID 2389245Notes

Reaction equation

HRID 2389245 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].Cl[C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([N:18]2[CH2:23][CH2:22][CH:21]([N:24]([CH3:32])[C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:20][CH2:19]2)=[N:10][N:9]=1.[CH3:33][N:34]1[C:38](B2OC(C)(C)C(C)(C)O2)=[CH:37][CH:36]=[N:35]1.C1(C)C=CC=CC=1>ClCCl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.C(O)C>[CH3:32][N:24]([CH:21]1[CH2:22][CH2:23][N:18]([C:11]2[C:12]3[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:8]([C:38]3[N:34]([CH3:33])[N:35]=[CH:36][CH:37]=3)=[N:9][N:10]=2)[CH2:19][CH2:20]1)[C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28]

Participants

9

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 49129081-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 58157124tert-Butyl 1-(4-chlorophthalazin-1-yl)piperidin-4-yl(methyl)carbamate

Product 1

HCID 59627389tert-butyl methyl(1-(4-(1-methyl-1H-pyrazol-5-yl)phthalazin-1-yl)piperidin-4-yl)carbamateYield 1,261.5%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Place sodium carbonate (3.82 g, 36.09 mmol), tert-butyl 1-(4-chlorophthalazin-1-yl)piperidin-4-yl(methyl)carbamate (6.8 g, 18.04 mmol) and 1-methyl-1H-pyrazole-5-boronic acid pinacol ester (5.63 g, 27 1 mmol) in a flask with a mixture of toluene (50 mL), ethanol (17 mL), and water (17 mL). Degas the mixture for 10 min with nitrogen gas. Add tetrakis(triphenylphosphine)palladium (0.4 g, 0.35 mmol) and heat the mixture at 74° C. overnight. Cool the mixture to ambient temperature and dilute with dichloromethane. Wash the organic portion with brine, dry over Na2SO4, and concentrate under reduced pressure. Purify the resulting residue by flash silica gel chromatography (hexane:ethyl acetate:2 M NH3 in MeOH=20:5:1) to provide the title compound as a yellow foam (5.33 g, 70%). ES/MS m/z 423.2 (M+1).

Workup

  1. customDegas the mixture for 10 min with nitrogen gas
  2. washWash the organic portion with brine
  3. dry with materialdry over Na2SO4
  4. concentrationconcentrate under reduced pressure
  5. customPurify the resulting residue by flash silica gel chromatography (hexane:ethyl acetate:2 M NH3 in MeOH=20:5:1)

Sources & evidence

ORD record
ord-85ca032435f24000ad06466026993405
Source dataset
uspto-grants-2012_09
Patent number
US08273742B2

Reaction notes

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