Cesium carbonate → 2-Methyl-5-(pyridin-3-ylamino)-thiazole-4-carboxylic acid ethyl ester

HRID 2244398Notes

Reaction equation

HRID 2244398 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([CH3:12])[S:9][C:10]=1[NH2:11])=[O:5])[CH3:2].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.Br[C:56]1[CH:57]=[N:58][CH:59]=[CH:60][CH:61]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1COCC1.O1CCOCC1>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([CH3:12])[S:9][C:10]=1[NH:11][C:56]1[CH:57]=[N:58][CH:59]=[CH:60][CH:61]=1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 122863-BromopyridineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 13329095Ethyl 5-amino-2-methylthiazole-4-carboxylate

Product 1

HCID 684061872-Methyl-5-(pyridin-3-ylamino)-thiazole-4-carboxylic acid ethyl esterYield 65%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

A Schlenck flask was charged with 5-amino-2-methyl-thiazole-4-carboxylic acid ethyl ester (0.33 g, 1.80 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos) (0.15 g, 0.26 mmol) and palladium dibenzylideneacetone (Pd2dba3)-chloroform complex (0.08 g, 0.08 mmol). Degassed dioxane (6.00 ml) was added, followed by 3-bromopyridine (0.23 g, 1.50 mmol). The flask was subjected to 5 cycles of evacuation and backfiring with argon. The reaction mixture was then transferred under argon to a microwave vial containing cesium carbonate (0.84 g, 2.60 mmol). The vial was then irradiated in a microwave oven at 150° C. for 10 min. The mixture was diluted with THF and the solids filtered, washing with THF. The filtrate was evaporated and the residue purified by flash chromatography (ethyl acetate/methanol) to yield 2-methyl-5-(pyridin-3-ylamino)-thiazole-4-carboxylic acid ethyl ester (0.25 g, 65%) as a light yellow solid, MS (ISP): m/e=264.1 (M+H+).

Workup

  1. customThe vial was then irradiated in a microwave oven at 150° C. for 10 min
  2. filtrationthe solids filtered
  3. washwashing with THF
  4. customThe filtrate was evaporated
  5. customthe residue purified by flash chromatography (ethyl acetate/methanol)

Sources & evidence

ORD record
ord-db2ccc11648a4901b9261e5e140646e6
Source dataset
uspto-grants-2010_03
Patent number
US07678815B2

Reaction notes

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