Cesium carbonate → Methyl 2-(6-{[(ethylamino)carbonyl]amino}pyridin-3-yl)-1,3-thiazole-5-carboxylate

HRID 2243019Notes

Reaction equation

HRID 2243019 reaction equation
[CH2:1]([NH:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10](B2OC(C)(C)C(C)(C)O2)=[CH:9][N:8]=1)=[O:5])[CH3:2].Br[C:23]1[S:24][C:25]([C:28]([O:30][CH3:31])=[O:29])=[CH:26][N:27]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>>[CH2:1]([NH:3][C:4]([NH:6][C:7]1[N:8]=[CH:9][C:10]([C:23]2[S:24][C:25]([C:28]([O:30][CH3:31])=[O:29])=[CH:26][N:27]=2)=[CH:11][CH:12]=1)=[O:5])[CH3:2]

Participants

4

Reactant 3

HCID 10796Cesium carbonateHCID 2773502Methyl 2-bromothiazole-5-carboxylateHCID 592084346-(3-Ethylureido)pyridine-3-boronic acid pinacol ester2×

Product 1

HCID 59208451Methyl 2-(6-{[(ethylamino)carbonyl]amino}pyridin-3-yl)-1,3-thiazole-5-carboxylate

Procedure

N-Ethyl-N′-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]urea (Intermediate 1, 0.20 g, 0.69 mmol), methyl 2-bromo-1,3-thiazole-5-carboxylate (0.152 g, 0.69 mmol), tetrakis triphenyl phosphine palladium (0.08 g, 0.069 mmol), and cesium carbonate (0.245 mg, 0.754 mmol) were taken in a microwave vial and degassed with argon. Then dioxane:water (4:1, 3 mL) was added to it and microwaved at 110° C. for half an hour. The reaction mixture was partitioned between water and EtOAc and layers separated. The organic layer was washed with sat. sodium bicarbonate solution, water, brine and dried over magnesium sulfate. The solvent was removed and the residue was purified by flash chromatography eluting with 2% MeOH in DCM to 3% MeOH in DCM. MS (ESP): 307 (M+H+) for C13H14N4O3S; NMR: 1.09 (t, 3H), 3.16-3.22 (m, 2H), 3.86 (s, 3H), 7.60 (d, 1H), 7.79 (t, 1H), 8.27 (dd, 1H), 8.49 (s, 1H), 8.83 (s, 1H), 9.56 (s, 1H).

Workup

  1. customdegassed with argon
  2. additionThen dioxane:water (4:1, 3 mL) was added to it
  3. custommicrowaved at 110° C. for half an hour
  4. customThe reaction mixture was partitioned between water and EtOAc and layers
  5. customseparated
  6. washThe organic layer was washed with sat. sodium bicarbonate solution, water, brine
  7. dry with materialdried over magnesium sulfate
  8. customThe solvent was removed
  9. customthe residue was purified by flash chromatography
  10. washeluting with 2% MeOH in DCM to 3% MeOH in DCM

Sources & evidence

ORD record
ord-21813cabaf7b407d8de1f1a8941940cb
Source dataset
uspto-grants-2010_03
Patent number
US07674801B2

Reaction notes

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