Potassium Carbonate → (S)-tert-Butyl 2-((S)-1-amino-3-(4-(6-cyanopyridin-3-yl)phenyl)-1-oxopropan-2-ylcarbamoyl)piperidine-1-carboxylate

HRID 600316Notes

Reaction equation

HRID 600316 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:39]=[CH:40][C:41]([C:44]#[N:45])=[N:42][CH:43]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O>[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]=[N:42][C:41]([C:44]#[N:45])=[CH:40][CH:39]=2)=[CH:7][CH:6]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 8171545-Bromopyridine-2-carbonitrileHCID 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-carboxylate

Product 1

HCID 57999648(S)-tert-Butyl 2-((S)-1-amino-3-(4-(6-cyanopyridin-3-yl)phenyl)-1-oxopropan-2-ylcarbamoyl)piperidine-1-carboxylateYield 79.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent2×

Procedure

A solution 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 (0.150 g) in dioxane (1 mL) was added to a stirred solution of 5-bromopicolinonitrile (0.055 g) and bis[bis(1,2-diphenylphosphino)ethane]palladium (0) (0.003 g) in dioxane (1 mL) under nitrogen. The resulting mixture was stirred for 10 min. A solution of potassium carbonate (0.124 g) in water (0.75 mL) was added and the resulting solution was stirred at 75° C. for 16 h. The cooled mixture was evaporated to dryness. The residue was taken up in ethyl acetate and washed with saturated brine, dried over sodium sulfate and adsorbed onto silica. The crude product was purified by flash silica chromatography, eluting with 3:1 ethyl acetate/isohexane). Pure fractions were evaporated to dryness to afford the subtitle compound (0.113 g).

Workup

  1. stirringthe resulting solution was stirred at 75° C. for 16 h
  2. customThe cooled mixture was evaporated to dryness
  3. washwashed with saturated brine
  4. dry with materialdried over sodium sulfate
  5. customThe crude product was purified by flash silica chromatography
  6. washeluting with 3:1 ethyl acetate/isohexane)
  7. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-a5b49953c7bf43ff903db367a6fe3e9b
Source dataset
uspto-grants-2011_03
Patent number
US07902181B2

Reaction notes

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