3-Pyridinylboronic acid → HCID 86629521, compound

HRID 1711157Notes

Reaction equation

HRID 1711157 reaction equation
Cl[C:2]1[CH:27]=[C:26]([CH3:28])[C:5]([C:6]([NH:8][CH2:9][CH2:10][C@H:11]([N:13]2[CH2:18][CH2:17][CH:16]([NH:19][CH2:20][C:21]3[CH:25]=[CH:24][S:23][CH:22]=3)[CH2:15][CH2:14]2)[CH3:12])=[O:7])=[C:4]([CH3:29])[N:3]=1.[N:30]1[CH:35]=[CH:34][CH:33]=[C:32](B(O)O)[CH:31]=1>COCCOC.C(Cl)Cl.C([O-])(O)=O.[Na+].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>[S:23]1[CH:24]=[CH:25][C:21]([CH2:20][NH:19][CH:16]2[CH2:17][CH2:18][N:13]([C@H:11]([CH3:12])[CH2:10][CH2:9][NH:8][C:6]([C:5]3[C:26]([CH3:28])=[CH:27][C:2]([C:32]4[CH:31]=[N:30][CH:35]=[CH:34][CH:33]=4)=[N:3][C:4]=3[CH3:29])=[O:7])[CH2:14][CH2:15]2)=[CH:22]1

Participants

7

Reactant 2

HCID 27343783-Pyridinylboronic acidHCID 86629522HCID 86629522, compound

Product 1

HCID 86629521HCID 86629521, compound

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
90 °C

Procedure

To an argon-degassed solution of 6-chloro-2,4-dimethyl-N—((R)-3-{4-[(thiophen-3-ylmethyl)-amino]-piperidin-1-yl}-butyl)-nicotinamide (100 mg, 0.23 mmol) and 3-pyridine boronic acid (56 mg, 0.46 mmol) in DME/2 M Na2CO3 (5:2, 3.5 ml) was added Pd(PPh3)4 (15 mg, 0.013 mmol) and the reaction stirred at 90° C. overnight. The mixture was cooled, diluted with CH2Cl2 (25 ml) and saturated aqueous NaHCO3 (25 ml). The aqueous layer was extracted with CH2Cl2 (2×10 ml) and the combined organic extracts were dried (Na2SO4), concentrated and purified by column chromatography on silica gel (CH2Cl2MeOH/NH4OH, 96:4:0 then 88:10:2) to afford 4,6-dimethyl-[2,3′]bipyridinyl-5-carboxylic acid ((R)-3-{4-[(thiophen-3-ylmethyl)-amino]-piperidin-1-yl}-butyl)-amide as a mixture of product and starting amine (˜25%).

Workup

  1. temperatureThe mixture was cooled
  2. extractionThe aqueous layer was extracted with CH2Cl2 (2×10 ml)
  3. dry with materialthe combined organic extracts were dried (Na2SO4)
  4. concentrationconcentrated
  5. custompurified by column chromatography on silica gel (CH2Cl2MeOH/NH4OH, 96:4:0

Sources & evidence

ORD record
ord-c25723d5931d449c926d51d1e379bea8
Source dataset
uspto-grants-2010_09
Patent number
US07790747B2

Reaction notes

Loading…