Potassium Phosphate, Tribasic → (3aR,6aR)-4'-(5-Methyl-hexahydro-pyrrolo[3,4-b]pyrrol-1-yl)-biphenyl-4-carbonitrile

HRID 12953

Reaction equation

HRID 12953 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:12][CH2:11][C@@H:10]3[CH2:13][N:14]([CH3:16])[CH2:15][C@H:9]23)=[CH:4][CH:3]=1.[C:17]([C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1)#[N:18].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(O)(C)C>[CH3:16][N:14]1[CH2:13][C@@H:10]2[C@@H:9]([N:8]([C:5]3[CH:6]=[CH:7][C:2]([C:22]4[CH:23]=[CH:24][C:19]([C:17]#[N:18])=[CH:20][CH:21]=4)=[CH:3][CH:4]=3)[CH2:12][CH2:11]2)[CH2:15]1

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 27343264-Cyanophenylboronic acidHCID 44221503(3aR,6aR)-1-(4-Bromophenyl)-5-methyloctahydropyrrolo[3,4-b]pyrrole

Product 1

HCID 16733807(3aR,6aR)-4'-(5-Methyl-hexahydro-pyrrolo[3,4-b]pyrrol-1-yl)-biphenyl-4-carbonitrileYield 71.3%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
60 °C

Procedure

The product of Example 7C (30.0 mg, 0.11 mmole), 4-cyanophenylboronic acid (18.8 mg, 0.13 mmole), palladium(II) acetate (1.2 mg, 0.005 mmole), 2-(dicyclohexylphosphino)biphenyl (3.8 mg, 0.01 mmole) and potassium phosphate (K3PO4) (75 mg, 0.35 mmole) were dissolved in 1 ml of toluene, 0.5 ml of isopropanol and 0.5 ml of water. The mixture was stirred at 60° C. under N2 for 5 hours. The mixture was cooled to room temperature, diluted with water and extracted with dichloromethane (5×). The combined organics were dried over sodium sulfate, filtered and concentrated and purified by chromatography (eluting with a mixture of 5% methanol in dichloromethane) to provide the title compound (23.1 mg, 71.3%). 1H NMR (300 MHz, CDCl3) δ ppm 7.60-7.68 (m, 4H) 7.47-7.53 (m, 2H) 6.61-6.68 (m, 2H) 4.14-4.22 (m, 1H) 3.51-3.60 (m, 1H) 3.28-3.35 (m, 1H) 2.93-3.01 (m, 1H) 2.71-2.75 (m, 1H) 2.48-2.61 (m, 3H) 2.32 (s, 3H) 2.14-2.25 (m, 1H) 1.96 (d, J=7.12 Hz, 1H). MS; (M+H)+=281/283.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionextracted with dichloromethane (5×)
  3. dry with materialThe combined organics were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by chromatography (
  7. washeluting with a mixture of 5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-c8e2b517eba34eabab89737cbc0038da
Source dataset
uspto-grants-2010_06
Patent number
US07728031B2

Linked notes

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