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

HRID 2243031Notes

Reaction equation

HRID 2243031 reaction equation
Cl[C:2]1[S:3][C:4]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[C:5]([C:7](=[O:12])[NH:8][CH:9]([CH3:11])[CH3:10])[N:6]=1.[CH2:18]([NH:20][C:21]([NH:23][C:24]1[CH:29]=[CH:28][C:27](B2OC(C)(C)C(C)(C)O2)=[CH:26][N:25]=1)=[O:22])[CH3:19].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>[CH2:18]([NH:20][C:21](=[O:22])[NH:23][C:24]1[N:25]=[CH:26][C:27]([C:2]2[S:3][C:4]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[C:5]([C:7](=[O:12])[NH:8][CH:9]([CH3:11])[CH3:10])[N:6]=2)=[CH:28][CH:29]=1)[CH3:19]

Participants

8

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 592084346-(3-Ethylureido)pyridine-3-boronic acid pinacol ester2×HCID 59208444Ethyl 2-chloro-4-isopropylcarbamoyl-thiazole-5-carboxylate2×

Product 1

HCID 59208404Ethyl 2-[6-(3-ethyl-ureido)-pyridin-3-yl]-4-isopropylcarbamoyl-thiazole-5-carboxylateYield 17.72%

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, ethyl 2-chloro-4-isopropylcarbamoyl-thiazole-5-carboxylate (Intermediate 28, 1.1 g, 3.97 mmol), N-ethyl-N′-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-yl]-urea (Intermediate 1, 1.15 g, 3.97 mmol), cesium carbonate (1.29 g, 3.97 mmol), Tetrakis (triphenylphosphino) palladium (0) (0.458 g, 0.397 mmol) in 15 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, then concentrated under reduced pressure to yield crude a residue which was purified by column chromatography over silica gel to afford 0.195 g (17.72%) of the title compound as solid. MS (APCI): 406 (M+H−) for C18H23N5O4S; NMR: 1.13 (t, 3H), δ 1.16 (d, 6H), 1.28 (t, 3H), δ 3.2 (q, 2H), 4.04 (m, 1H), 4.29 (q, 2H), 7.63 (d, 1H), 7.70 (br s, 1H), 8.27 (dd, 1H), δ 8.45 (d, 1H), 8.83 (d, 1H), 9.56 (s, 1H).

Workup

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

Sources & evidence

ORD record
ord-01f73cd47cc241c68edf6585b3082a5e
Source dataset
uspto-grants-2010_03
Patent number
US07674801B2

Reaction notes

Loading…