Potassium Phosphate, Tribasic → HCID 118251098, compound

HRID 2283459Notes

Reaction equation

HRID 2283459 reaction equation
[N:1]1[CH:6]=[CH:5][C:4](B(O)O)=[CH:3][CH:2]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:19]1[CH:20]=[C:21]([NH:27][C@@H:28]2[CH2:33][CH2:32][CH2:31][N:30]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:29]2)[C:22]([O:25][CH3:26])=[N:23][CH:24]=1>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:26][O:25][C:22]1[N:23]=[CH:24][C:19]([C:4]2[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=2)=[CH:20][C:21]=1[NH:27][C@@H:28]1[CH2:33][CH2:32][CH2:31][N:30]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:29]1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 2734379(Pyridin-4-yl)boronic acidHCID 118251036HCID 118251036, compound

Product 1

HCID 118251098HCID 118251098, compoundYield 50.2%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Pyridine-4-boronic acid (0.950 g, 7.77 mmol) and potassium phosphate (2 M, 70 mL) was added to a solution of (R)-tert-butyl 3-((5-bromo-2-methoxypyridin-3-yl)amino)piperidine-1-carboxylate (2.00 g, 5.18 mmol) in dioxane (70 mL). The mixture was degassed for 20 min and then Pd(dppf)Cl2 (1.28 g, 1.55 mmol) was added. The mixture was stirred at 80° C. for 6 h. The mixture was allowed to cool to room temperature and was filtered through celite and concentrated. The residue was purified by chromatography using 40-50% ethyl acetate in pet ether to give 1 g of the desired compound: 1H NMR (300 MHz, DMSO-d6) 8.55-8.65 (narrow m, 2H), 7.85 (s, 1H), 7.65-7.75 (narrow m, 2H), 7.10-7.30 (m, 1H), 5.03 (br s, 1H), 3.94 (s, 3H), 3.45-3.80 (m, 3H), 2.90-3.15 (m, 2H), 1.85-2.00 (m, 1H), 1.15-1.75 (m, 12H); MS (ES) m/z 385 (M+H).

Workup

  1. customThe mixture was degassed for 20 min
  2. temperatureto cool to room temperature
  3. filtrationwas filtered through celite
  4. concentrationconcentrated
  5. customThe residue was purified by chromatography

Sources & evidence

ORD record
ord-4888b6040b0e4368a8ee12753ac0d42c
Source dataset
uspto-grants-2015_09
Patent number
US09145393B2

Reaction notes

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