Sodium Carbonate → 1,1-Dimethylethyl 4-[(6-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-1,2-benzisoxazol-3-yl)acetyl]-1-piperazinecarboxylate

HRID 1988892Notes

Reaction equation

HRID 1988892 reaction equation
Br[C:2]1[CH:26]=[CH:25][C:5]2[C:6]([CH2:9][C:10]([N:12]3[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]3)=[O:11])=[N:7][O:8][C:4]=2[CH:3]=1.[CH:27]1([NH:30][C:31](=[O:48])[C:32]2[CH:37]=[CH:36][C:35]([CH3:38])=[C:34](B3OC(C)(C)C(C)(C)O3)[CH:33]=2)[CH2:29][CH2:28]1.C(=O)([O-])[O-].[Na+].[Na+]>C(O)(C)C.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>[CH:27]1([NH:30][C:31]([C:32]2[CH:37]=[CH:36][C:35]([CH3:38])=[C:34]([C:2]3[CH:26]=[CH:25][C:5]4[C:6]([CH2:9][C:10]([N:12]5[CH2:13][CH2:14][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:16][CH2:17]5)=[O:11])=[N:7][O:8][C:4]=4[CH:3]=3)[CH:33]=2)=[O:48])[CH2:28][CH2:29]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 21914577N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide2×HCID 586564751,1-Dimethylethyl 4-[(6-bromo-1,2-benzisoxazol-3-yl)acetyl]-1-piperazinecarboxylate2×

Product 1

HCID 586565191,1-Dimethylethyl 4-[(6-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-1,2-benzisoxazol-3-yl)acetyl]-1-piperazinecarboxylateYield 58.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 3776IsopropanolSolvent

Procedure

A mixture of 1,1-dimethylethyl 4-[(6-bromo-1,2-benzisoxazol-3-yl)acetyl]-1-piperazinecarboxylate (Intermediate 33) (0.045 g) N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (Intermediate 5) (0.03 g) and 2M aqueous sodium carbonate (0.65 ml) in isopropanol (2.5 ml) under nitrogen was treated with tetrakis(triphenylphosphine)palladium(0) (1 mg) then stirred at reflux for 18 h. On cooling the mixture was absorbed onto silica (Merck 7734) and applied to a Varian Bond-Elut SPE cartridge (silica, 5 g). Sequential elution with dichloromethane, chloroform, ether, ethyl acetate, acetonitrile and acetone yielded the title compound as a white solid (0.03 g).

Workup

  1. temperatureat reflux for 18 h
  2. temperatureOn cooling the mixture
  3. customwas absorbed onto silica (Merck 7734)
  4. washSequential elution with dichloromethane, chloroform, ether, ethyl acetate, acetonitrile and acetone

Sources & evidence

ORD record
ord-c5e8076ead2642f0a9085b85cebfb8c4
Source dataset
uspto-grants-2010_01
Patent number
US07642276B2

Reaction notes

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