2-Methoxyphenylboronic acid → (3-{[2-(2'-Methoxy-biphenyl-2-ylamino)-ethylamino]-methyl}-phenyl)-piperidin-1-yl-methanone

HRID 606666Notes

Reaction equation

HRID 606666 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][CH2:9][CH2:10][NH:11][CH2:12][C:13]1[CH:14]=[C:15]([C:19]([N:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)=[O:20])[CH:16]=[CH:17][CH:18]=1.[CH3:27][O:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1B(O)O>C([O-])([O-])=O.[Na+].[Na+].CCO.C1(C)C=CC=CC=1.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>[CH3:27][O:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][CH2:9][CH2:10][NH:11][CH2:12][C:13]1[CH:14]=[C:15]([C:19]([N:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)=[O:20])[CH:16]=[CH:17][CH:18]=1

Participants

5

Reactant 2

HCID 27339582-Methoxyphenylboronic acidHCID 58975554(3-{[2-(2-Bromo-phenylamino)-ethylamino]-methyl}-phenyl)-piperidin-1-yl-methanone

Product 1

HCID 58975557(3-{[2-(2'-Methoxy-biphenyl-2-ylamino)-ethylamino]-methyl}-phenyl)-piperidin-1-yl-methanoneYield 31.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 18778779HCID 18778779, compoundSolvent

Procedure

To a solution of (3-{[2-(2-bromo-phenylamino)-ethylamino]-methyl}-phenyl)piperidin-1-yl-methanone (Example 17; 0.051 g, 0.12 mmol) and 2-methoxybenzeneboronic acid (0.037 g, 0.25 mmol) in 2 M Na2CO3/EtOH/toluene (1:1:4, 6 mL) was added Pd(PPh3)4 (0.014 g, 0.012 mmol), and the resulting solution was stirred at reflux for 16 h. The solution was partitioned with EtOAc (20 mL) and satd aqueous NaHCO3 (20 mL), and the aqueous layer was back-extracted with EtOAc (3×30 mL). The combined organic layers were washed with brine, dried (MgSO4), filtered, and concentrated under reduced pressure. The crude residue was purified by preparative TLC (10% CH3OH/CH2Cl2) to provide a tan oil (0.0168 g, 28%). MS (ESI): mass calculated for C28H33N3O2, 443.26; m/z found, 444.2 [M+H]+, 466.2 [M+Na]+. 1H NMR (400 MHz, CDCl3): 7.38-7.22 (m, 7H), 7.08-6.97 (m, 3H), 6.78-6.72 (br s, 2H), 4.15 (br s, 1H), 3.69-3.76 (br m, 4H), 3.68 (s, 3H), 3.29-3.24 (br m, 4H), 2.86-2.76 (m, 2H), 1.75-1.49 (br m, 8H). 13C NMR (100 MHz, CDCl3): 170.2, 156.8, 145.8, 140.4, 136.5, 131.9, 130.7, 129.0, 128.9, 128.6, 128.4, 128.0, 126.4, 125.3, 124.9, 121.1, 116.8, 111.2, 110.5, 55.6, 53.2, 48.7, 47.8, 43.5, 43.6, 26.5, 25.6, 24.5.

Workup

  1. temperatureat reflux for 16 h
  2. customThe solution was partitioned with EtOAc (20 mL)
  3. extractionthe aqueous layer was back-extracted with EtOAc (3×30 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude residue was purified by preparative TLC (10% CH3OH/CH2Cl2)

Sources & evidence

ORD record
ord-8156bfc67ba54be9819311081cc26b83
Source dataset
uspto-grants-2011_03
Patent number
US07915420B2

Reaction notes

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