Pyridine-2-boronic acid → HCID 44546549, compound

HRID 1888608Notes

Reaction equation

HRID 1888608 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1B(O)O.Br[C:11]1[N:19]=[CH:18][C:17]2[NH:16][C:15]3[N:20]=[CH:21][C:22]([C:24]4[CH:29]=[CH:28][C:27]([CH2:30][N:31]5[CH2:36][CH2:35][CH:34]([C:37]([F:40])([F:39])[F:38])[CH2:33][CH2:32]5)=[CH:26][CH:25]=4)=[CH:23][C:14]=3[C:13]=2[CH:12]=1>C(#N)C.C(=O)([O-])[O-].[Na+].[Na+]>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:11]2[N:19]=[CH:18][C:17]3[NH:16][C:15]4[N:20]=[CH:21][C:22]([C:24]5[CH:25]=[CH:26][C:27]([CH2:30][N:31]6[CH2:32][CH2:33][CH:34]([C:37]([F:38])([F:40])[F:39])[CH2:35][CH2:36]6)=[CH:28][CH:29]=5)=[CH:23][C:14]=4[C:13]=3[CH:12]=2)[CH:2]=1

Participants

5

Reactant 2

HCID 2762745Pyridine-2-boronic acidHCID 58266798HCID 58266798, compound

Product 1

HCID 44546549HCID 44546549, compoundYield 11.2%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
140 °C

Procedure

To a mixture of pyridine-2-boronic acid (27 mg, 0.22 mmol), 6-bromo-3-[4-(4-trifluoromethyl-piperidin-1-ylmethyl)-phenyl]-9H-dipyrido[2,3-b;4′,3′-d]pyrrole (55 mg, 0.11 mmol) and 1,1′-[bis(diphenylphosphino)ferrocene]-dichloropalladium(II) (9 mg, 0.011 mmol) in acetonitrile (1 mL) and saturated aqueous sodium carbonate solution (1 mL) was heated under microwave irradiation at 140° C. for 30 minutes. The cooled reaction mixture was partitioned between DCM and water and the phases were separated using a hydrophobic fit and the organic phase evaporated. The residue was purified HPLC (C18 column, 50-98% MeCN in water (containing 20 mM triethylamine) over 30 minutes and the fractions containing pure product combined and concentrated then freeze-dried to afford the title compound (6 mg, 11%). 1H NMR (CDCl3 plus CD3OD, 400 MHz): 9.22 (dd, J=2.3, 0.8 Hz, 1H), 9.05 (d, J=1.1 Hz, 1H), 8.86-8.83 (m, 2H), 8.59-8.56 (m, 2H), 8.48-8.44 (m, 1H), 7.73-7.69 (m, 2H), 7.58-7.54 (m, 1H), 7.50 (d, J=8.0Hz, 2H), 3.64 (s, 2H), 3.11-3.03 (m, 2H), 2.17-2.04 (m, 3H), 1.93-1.85 (m, 2H), 1.74-1.61 (m, 2H). LCMS (Method A): RT=5.43 min, M+H+=488.

Workup

  1. customThe cooled reaction mixture
  2. customwas partitioned between DCM and water
  3. customthe phases were separated
  4. customthe organic phase evaporated
  5. customThe residue was purified HPLC (C18 column, 50-98% MeCN in water (containing 20 mM triethylamine) over 30 minutes
  6. additionthe fractions containing pure product
  7. concentrationconcentrated
  8. customthen freeze-dried

Sources & evidence

ORD record
ord-f24cda1818594bffa40bfdc6d221dada
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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