3-Pyridinemethanamine → 2-Bromo-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide

HRID 1879181Notes

Reaction equation

HRID 1879181 reaction equation
[Br:1][C:2]1[S:3][C:4]([C:8]([OH:10])=O)=[C:5]([CH3:7])[N:6]=1.[NH2:11][CH2:12][C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[N:15]1[CH:16]=[CH:17][CH:18]=[C:13]([CH2:12][NH:11][C:8]([C:4]2[S:3][C:2]([Br:1])=[N:6][C:5]=2[CH3:7])=[O:10])[CH:14]=1

Participants

6

Reactant 4

HCID 310183-PyridinemethanamineHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 28240582-Bromo-4-methyl-1,3-thiazole-5-carboxylic acid

Product 1

HCID 666315502-Bromo-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamideYield 96.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-bromo-4-methyl-thiazole-5-carboxylic acid (10.0 g, 45.0 mmol) in methylene chloride (200 mL) was added 3-(aminomethyl) pyridine (5.05 mL, 49.5 mmol), benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP reagent, 21.9 g, 49.5 mmol) and N,N-diisopropylethylamine (15.7 mL, 90.1 mmol). The mixture was stirred under nitrogen at room temperature for 16 hr, then diluted with methylene chloride (300 mL), washed with water (300 mL) and brine (2×200 mL). The organic phase was dried (Na2SO4) and evaporated. The residue was purified by flash chromatography over silica gel (methylene chloride:methanol, 95:5) to provide 2-bromo-4-methyl-thiazole-5-carboxylic acid (pyridine-3-ylmethyl)-amide as a yellow solid (13.5 g, 96% yield). MS (M+H)+=313; Rt=1.01 min.

Workup

  1. washwashed with water (300 mL) and brine (2×200 mL)
  2. dry with materialThe organic phase was dried (Na2SO4)
  3. customevaporated
  4. customThe residue was purified by flash chromatography over silica gel (methylene chloride:methanol, 95:5)

Sources & evidence

ORD record
ord-a653da8735ee46c3b37fbb222d15bdc5
Source dataset
uspto-grants-2012_11
Patent number
US08314138B2

Reaction notes

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