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

HRID 1466220Notes

Reaction equation

HRID 1466220 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([N:12]2[CH2:17][CH2:16][CH:15]([N:18]([CH3:26])[C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH2:14][CH2:13]2)=[N:4][N:3]=1.[CH3:27][N:28]1[C:32](B2OC(C)(C)C(C)(C)O2)=[CH:31][CH:30]=[N:29]1.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>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>[CH3:26][N:18]([CH:15]1[CH2:16][CH2:17][N:12]([C:5]2[C:6]3[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=3)[C:2]([C:32]3[N:28]([CH3:27])[N:29]=[CH:30][CH:31]=3)=[N:3][N:4]=2)[CH2:13][CH2:14]1)[C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22]

Participants

8

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 49129081-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 59627406tert-Butyl 1-(4-bromophthalazin-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 69%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

Charge a reaction tube with tert-butyl 1-(4-bromophthalazin-1-yl)piperidin-4-yl(methyl)carbamate (500 mg, 1.2 mmol), 1-methyl-1H-pyrazole-5-boronic acid pinacol ester (370 mg, 1.8 mmol), sodium carbonate (252 mg, 2.4 mmol), toluene (3.75 mL), ethanol (1.25 mL), and water (1.25 mL). Degas the reaction mixture with nitrogen for 10 min. Add tetrakis(triphenylphosphine)palladium (137.1 mg, 118.7 μmol). Bubble nitrogen through the reaction mixture for another 10 min. Cap the reaction vial and heat at 90° C. overnight. Cool the reaction and filter through a silica gel pad eluting with 5% MeOH:CH2Cl2. Concentrate the fractions under reduced pressure. Purify the resulting residue using silica gel chromatography (2% 2 N NH3 in MeOH:CH2Cl2) to obtain the final product (345.6 mg, 69%). ES/MS m/z 423.2 (M+1).

Workup

  1. customDegas the reaction mixture with nitrogen for 10 min
  2. customCap
  3. customthe reaction vial
  4. temperatureCool
  5. customthe reaction
  6. filtrationfilter through a silica gel pad
  7. washeluting with 5% MeOH
  8. concentrationConcentrate the fractions under reduced pressure
  9. customPurify the resulting residue

Sources & evidence

ORD record
ord-c122fa4714394f2ca80295c90279e657
Source dataset
uspto-grants-2015_04
Patent number
US09000023B2

Reaction notes

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