Diisopropylethylamine → 5-bromo-N-((2'-fluoro-2,4'-bipyridin-5-yl)methyl)picolinamide

HRID 711245Notes

Reaction equation

HRID 711245 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([OH:10])=O)=[N:6][CH:7]=1.[F:11][C:12]1[CH:17]=[C:16]([C:18]2[CH:23]=[CH:22][C:21]([CH2:24][NH2:25])=[CH:20][N:19]=2)[CH:15]=[CH:14][N:13]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:25][CH2:24][C:21]2[CH:22]=[CH:23][C:18]([C:16]3[CH:15]=[CH:14][N:13]=[C:12]([F:11])[CH:17]=3)=[N:19][CH:20]=2)=[O:10])=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 6085445-Bromopyridine-2-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67208618(2'-Fluoro-2,4'-bipyridin-5-yl)methanamine

Product 1

HCID 672086435-bromo-N-((2'-fluoro-2,4'-bipyridin-5-yl)methyl)picolinamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 5-bromopicolinic acid 38-3 (309 mg, 1.53 mmol), (2′-fluoro-2,4′-bipyridin-5-yl)methanamine 38-2 (312 mg, 1.53 mmol) and HATU (582 mg, 1.53 mmol) in DMF (7 mL) was added DIEA (0.76 mL, 4.59 mmol). The mixture was stirred at room temperature for 2 hours. The mixture was diluted with ethyl acetate (100 mL), washed with H2O and brine, dried over Na2SO4, and concentrated to dryness by rotary evaporation. The crude product was purified by silica gel flash chromatography, eluted with 5% methanol containing ˜7N ammonia in dichloromethane to give 5-bromo-N-((2′-fluoro-2,4′-bipyridin-5-yl)methyl)picolinamide 38-4 as yellow solid. MS m/z 387.1 (M+1)

Workup

  1. washwashed with H2O and brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated to dryness by rotary evaporation
  4. customThe crude product was purified by silica gel flash chromatography
  5. washeluted with 5% methanol containing ˜7N ammonia in dichloromethane

Sources & evidence

ORD record
ord-281196e8c3e24064933e183167d3829a
Source dataset
uspto-grants-2015_11
Patent number
US09181235B2

Reaction notes

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