Potassium Carbonate → N-benzyl-N-tert-butylcarbonyl-N-[(2S)-5-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]amine

HRID 420780Notes

Reaction equation

HRID 420780 reaction equation
FC(F)(F)S(O[C:7]1[C:16]2[CH2:15][CH2:14][C@H:13]([N:17]([CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:18]([C:20]([CH3:23])([CH3:22])[CH3:21])=[O:19])[CH2:12][C:11]=2[CH:10]=[CH:9][CH:8]=1)(=O)=O.[CH3:33][N:34]1[C:38]([CH3:39])=[C:37](B2OC(C)(C)C(C)(C)O2)[C:36]([CH3:49])=[N:35]1.C([O-])([O-])=O.[K+].[K+]>COCCOC.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>[CH2:24]([N:17]([C:18]([C:20]([CH3:23])([CH3:22])[CH3:21])=[O:19])[C@H:13]1[CH2:14][CH2:15][C:16]2[C:11](=[CH:10][CH:9]=[CH:8][C:7]=2[C:37]2[C:36]([CH3:49])=[N:35][N:34]([CH3:33])[C:38]=2[CH3:39])[CH2:12]1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27953111,3,5-Trimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 87093821(6S)-6-[Benzyl(tert-butylcarbonyl)amino]-5,6,7,8-tetrahydronaphthalen-1-yl trifluoromethanesulfonate

Product 1

HCID 66658895N-benzyl-N-tert-butylcarbonyl-N-[(2S)-5-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]amineYield 86%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

(6S)-6-[Benzyl(tert-butylcarbonyl)amino]-5,6,7,8-tetrahydronaphthalen-1-yl trifluoromethanesulfonate (0.5 g, 1.028 mmol), 1,3,5-trimethyl-1H-pyrazole-4-boronic acid pinacol ester (0.350 g, 1.482 mmol) and Pd(PPh3)4 (0.170 g, 0.147 mmol) were added to a solution of K2CO3 (0.30 g, 2.17 mmol) in a mixture of 1,2,-dimethoxyethane (30 mL) and H2O (4 mL). The reaction mixture was purged with N2 (g) for 10 min, and warmed up to reflux. The reaction was completed in 2 h. It was allowed to reach room temperature, diluted with AcOEt (300 mL) and filtered through Celite (washing with AcOEt). The organic layer was washed with brine (1×200 mL), dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by flash chromatography on silica gel (80-100% AcOEt/Hexane) to afford 0.38 g of the coupling product (Rf=0.1 (30% AcOEt/Hexane), viscous yellow oil, 83% yield).

Workup

  1. customThe reaction mixture was purged with N2 (g) for 10 min
  2. temperaturewarmed up
  3. temperatureto reflux
  4. customto reach room temperature
  5. additiondiluted with AcOEt (300 mL)
  6. filtrationfiltered through Celite (washing with AcOEt)
  7. washThe organic layer was washed with brine (1×200 mL)
  8. dry with materialdried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by flash chromatography on silica gel (80-100% AcOEt/Hexane)

Sources & evidence

ORD record
ord-893850c8669546b7ad57fc977c26c3b1
Source dataset
uspto-grants-2012_01
Patent number
US08097641B2

Reaction notes

Loading…