3-Aminopyridine → 2-Methyl-5-(pyridin-3-ylamino)-thiazole-4-carboxylic acid methyl ester

HRID 2244406Notes

Reaction equation

HRID 2244406 reaction equation
C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.[N:43]1[CH:48]=[CH:47][CH:46]=[C:45]([NH2:49])[CH:44]=1.[CH3:50][O:51][C:52]([C:54]1[N:55]=[C:56]([CH3:60])[S:57][C:58]=1Br)=[O:53].C(=O)([O-])[O-].[Cs+].[Cs+]>F[P-](F)(F)(F)(F)F.C([N+]1C=CN(C)C=1)CCC>[CH3:50][O:51][C:52]([C:54]1[N:55]=[C:56]([CH3:60])[S:57][C:58]=1[NH:49][C:45]1[CH:44]=[N:43][CH:48]=[CH:47][CH:46]=1)=[O:53]

Participants

6

Reactant 4

HCID 100093-AminopyridineHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 16427155Methyl 5-bromo-2-methyl-1,3-thiazole-4-carboxylate

Product 1

HCID 684063592-Methyl-5-(pyridin-3-ylamino)-thiazole-4-carboxylic acid methyl esterYield 94.3%

Reagents, catalysts & solvents 1

HCID 27341741-Butyl-3-methylimidazolium hexafluorophosphateCatalyst

Procedure

Dry dioxane (10.00 ml) was degassed by bubbling with argon in an ultrasonic bath, then added to a sealed microwave vial containing a mixture of 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos) (0.38 g, 0.66 mmol), palladium dibenzylideneacetone chloroform complex (0.21 g, 0.20 mmol), pyridin-3-ylamine (0.19 g, 2.00 mmol), 5-bromo-2-methyl-thiazole-4-carboxylic acid methyl ester (0.47 g, 2.00 mmol) and cesium carbonate (1.16 g, 6.00 mmol). The mixture was stirred for 10 min, then a few drops of 1-butyl-3-methylimidazolium hexafluorophosphate were added and the vial was irradiated in a microwave oven at 150° C. for 15 min. The volatiles were then removed under vacuum, and the residue was purified by flash chromatography (heptane/ethyl acetate), yielding 2-methyl-5-(pyridin-3-ylamino)-thiazole-4-carboxylic acid methyl ester (0.47 g, 94%), as a yellow solid, MS (ISP): m/e=250.1 (M+H+).

Workup

  1. customDry dioxane (10.00 ml) was degassed
  2. customby bubbling with argon in an ultrasonic bath
  3. additionadded to a sealed microwave vial
  4. additioncontaining
  5. customthe vial was irradiated in a microwave oven at 150° C. for 15 min
  6. customThe volatiles were then removed under vacuum
  7. customthe residue was purified by flash chromatography (heptane/ethyl acetate)

Sources & evidence

ORD record
ord-3509a262915e4466867a35269a9d8074
Source dataset
uspto-grants-2010_03
Patent number
US07678815B2

Reaction notes

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