Potassium Carbonate → 1,1-Dimethylethyl 4-({2'-fluoro-5'-[(methylamino)methyl]-3-biphenylyl}methyl)-1-piperazine carboxylate

HRID 657367Notes

Reaction equation

HRID 657367 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:9][NH:10][CH3:11])[CH:5]=[CH:6][C:7]=1[F:8].[CH3:12][C:13]([O:16][C:17]([N:19]1[CH2:24][CH2:23][N:22]([CH2:25][C:26]2[CH:27]=[C:28](B(O)O)[CH:29]=[CH:30][CH:31]=2)[CH2:21][CH2:20]1)=[O:18])([CH3:15])[CH3:14].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.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>[F:8][C:7]1[CH:6]=[CH:5][C:4]([CH2:9][NH:10][CH3:11])=[CH:3][C:2]=1[C:28]1[CH:29]=[CH:30][CH:31]=[C:26]([CH2:25][N:22]2[CH2:23][CH2:24][N:19]([C:17]([O:16][C:13]([CH3:15])([CH3:14])[CH3:12])=[O:18])[CH2:20][CH2:21]2)[CH:27]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 16781426[(3-Bromo-4-fluorophenyl)methyl](methyl)amineHCID 42609723(3-((4-(Tert-butoxycarbonyl)piperazin-1-yl)methyl)phenyl)boronic acid

Product 1

HCID 578134851,1-Dimethylethyl 4-({2'-fluoro-5'-[(methylamino)methyl]-3-biphenylyl}methyl)-1-piperazine carboxylateYield 66%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
150 °C

Procedure

To the solution of [(3-bromo-4-fluorophenyl)methyl]methylamine (0.52 g, 2.39 mmol) in p-dioxane/H2O (15/5 mL) was added {3-[(4-{[(1,1-dimethylethyl)oxy]carbonyl}-1-piperazinyl)methyl]phenyl}boronic acid (1.15 g, 3.60 mmol), Pd(PPh3)4 (139 mg, 0.12 mmol), and K2CO3 (1.33 g, 9.6 mmol). The result mixture was heated in a microwave machine at 150° C. for 15 mins. The organic layer was separated and concentrated. The residue was redissolved in EtOAc (˜70 mL), washed with H2O (20 mL), brine (20 mL), dried over Na2SO4, filtered, concentrated and purified by CombiFlash chomatograph to afford 0.65 g (66%) of the title compound. LC-MS m/z 414 (M+H)+.

Workup

  1. customThe organic layer was separated
  2. concentrationconcentrated
  3. dissolutionThe residue was redissolved in EtOAc (˜70 mL)
  4. washwashed with H2O (20 mL), brine (20 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by CombiFlash chomatograph

Sources & evidence

ORD record
ord-86d5f053579e42598aa3663074579461
Source dataset
uspto-grants-2011_12
Patent number
US08071588B2

Reaction notes

Loading…