Potassium Carbonate → (S)-tert-Butyl 2-((S)-1-amino-3-(4'-(cyanomethyl)-3'-(methylsulfonyl)biphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)piperidine-1-carboxylate

HRID 600336Notes

Reaction equation

HRID 600336 reaction equation
[NH2:1][C:2](=[O:36])[C@@H:3]([NH:20][C:21]([C@@H:23]1[CH2:28][CH2:27][CH2:26][CH2:25][N:24]1[C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[O:22])[CH2:4][C:5]1[CH:10]=[CH:9][C:8](B2OC(C)(C)C(C)(C)O2)=[CH:7][CH:6]=1.Br[C:38]1[CH:43]=[CH:42][C:41]([CH2:44][C:45]#[N:46])=[C:40]([S:47]([CH3:50])(=[O:49])=[O:48])[CH:39]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.[Pd].C1(P(C2C=CC=CC=2)CCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)CCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH2:1][C:2](=[O:36])[C@@H:3]([NH:20][C:21]([C@@H:23]1[CH2:28][CH2:27][CH2:26][CH2:25][N:24]1[C:29]([O:31][C:32]([CH3:33])([CH3:35])[CH3:34])=[O:30])=[O:22])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:38]2[CH:43]=[CH:42][C:41]([CH2:44][C:45]#[N:46])=[C:40]([S:47]([CH3:50])(=[O:49])=[O:48])[CH:39]=2)=[CH:7][CH:6]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 57999680(S)-tert-Butyl 2-((S)-1-amino-1-oxo-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-ylcarbamoyl)piperidine-1-carboxylateHCID 672691792-(4-Bromo-2-(methylsulfonyl)phenyl)acetonitrile

Product 1

HCID 57999668(S)-tert-Butyl 2-((S)-1-amino-3-(4'-(cyanomethyl)-3'-(methylsulfonyl)biphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)piperidine-1-carboxylateYield 76.7%

Reagents, catalysts & solvents 2

HCID 2724231Bis(1,2-bis(diphenylphosphino)ethane)palladium(0)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of (S)-tert-butyl 2-((S)-1-amino-1-oxo-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-ylcarbamoyl)piperidine-1-carboxylate (92 mg), 2-(4-bromo-2-(methylsulfonyl)phenyl)acetonitrile (75 mg), bis(1,2-bis(diphenylphosphino)ethane)-palladium(0) (8.29 mg, 9.17 μmol) and 2 N aqueous potassium carbonate (0.229 mL) in dioxane (3 mL) was heated at 75° C. for 14 h. The mixture was poured onto an Isolute HM-N cartridge, eluting with DCM, collecting about 100 mL of eluent. The eluent was concentrated in vacuo to leave a brown oil. The residue was purified by flash silica chromatography, eluting with ethyl acetate to give the subtitle compound as a white solid (80 mg).

Workup

  1. additionThe mixture was poured onto an Isolute HM-N cartridge
  2. washeluting with DCM
  3. customcollecting about 100 mL of eluent
  4. concentrationThe eluent was concentrated in vacuo
  5. customto leave a brown oil
  6. customThe residue was purified by flash silica chromatography
  7. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-5a30996f265e4b569cb305085d3cbd95
Source dataset
uspto-grants-2011_03
Patent number
US07902181B2

Reaction notes

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