Water → Ethyl 4-Dimethylcarbamoyl-2-[6-(3-ethyl-ureido)-pyridin-3-yl]-thiazole-5-carboxylate

HRID 2243026Notes

Reaction equation

HRID 2243026 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9](Cl)=[N:8][C:7]=1[C:12](=[O:16])[N:13]([CH3:15])[CH3:14])=[O:5])[CH3:2].[CH2:17]([NH:19][C:20]([NH:22][C:23]1[CH:28]=[CH:27][C:26](B2OC(C)(C)C(C)(C)O2)=[CH:25][N:24]=1)=[O:21])[CH3:18].C(=O)([O-])[O-].[Cs+].[Cs+].O>O1CCOCC1.C(OCC)(=O)C.C1(P([Pd-4](P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:14][N:13]([CH3:15])[C:12]([C:7]1[N:8]=[C:9]([C:26]2[CH:25]=[N:24][C:23]([NH:22][C:20]([NH:19][CH2:17][CH3:18])=[O:21])=[CH:28][CH:27]=2)[S:10][C:6]=1[C:4]([O:3][CH2:1][CH3:2])=[O:5])=[O:16]

Participants

8

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 59208397Ethyl 2-Chloro-4-dimethylcarbamoyl-thiazole-5-carboxylate2×HCID 592084346-(3-Ethylureido)pyridine-3-boronic acid pinacol ester

Product 1

HCID 25126467Ethyl 4-Dimethylcarbamoyl-2-[6-(3-ethyl-ureido)-pyridin-3-yl]-thiazole-5-carboxylateYield 36.5%

Reagents, catalysts & solvents 3

HCID 178420553HCID 178420553, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

In a 10 mL of microwave vial, 2-chloro-4-dimethylcarbamoyl-thiazole-5-carboxylic acid ethyl ester (Intermediate 26, 0.1 g, 0.37 mmol), N-ethyl-N′-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-yl]-urea (Intermediate1, 0.11 g, 0.37 mmol), cesium carbonate (0.12 g, 0.37 mmol), Tetrakis (triphenyl phosphino) palladium (0) (0.044 g, 0.037 mmol) in 4 mL of 4:1 dioxane:H2O was degassed for 30 min, then heated to 100° C. for 30 min. The reaction mixture was diluted with ethyl acetate (25 mL), then washed with water (10 mL). The organic layer was dried and concentrated to yield crude residue, which was purified by column chromatography over silica gel to afford 0.049 g (36.5%) of the title compound as a pale yellow solid. MS (APCI): 357 (M+H+) for C17H21N5O4S; NMR: δ 1.25 (t, 3H), δ 1.38 (t, 3H), δ 2.91 (s, 3H), δ 3.18 (s, 3H), δ 3.42 (q, 2H), δ 4.36 (q, 2H), δ 6.92 (d, 1H), δ 8.14 (d, 1H), δ 8.78 (d, 1H).

Workup

  1. washwashed with water (10 mL)
  2. customThe organic layer was dried
  3. concentrationconcentrated
  4. customto yield crude residue, which
  5. customwas purified by column chromatography over silica gel

Sources & evidence

ORD record
ord-cbe119a09ff742f183929175360e9c49
Source dataset
uspto-grants-2010_03
Patent number
US07674801B2

Reaction notes

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