Ethyl Acetate → HCID 59617693, compound

HRID 2061802Notes

Reaction equation

HRID 2061802 reaction equation
[CH2:1]([NH:3][C:4](=[O:24])[NH:5][C:6]1[N:11]=[CH:10][C:9](B(O)O)=[C:8]([C:15]2[S:16][CH:17]=[C:18]([C:20]([F:23])([F:22])[F:21])[N:19]=2)[CH:7]=1)[CH3:2].[CH2:25]([N:27]1[C:36]2[C:31](=[CH:32][CH:33]=[C:34](I)[CH:35]=2)[C:30](=[O:38])[C:29]([C:39]([O:41][CH2:42][CH3:43])=[O:40])=[CH:28]1)[CH3:26].C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>O1CCOCC1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:25]([N:27]1[C:36]2[C:31](=[CH:32][CH:33]=[C:34]([C:9]3[CH:10]=[N:11][C:6]([NH:5][C:4]([NH:3][CH2:1][CH3:2])=[O:24])=[CH:7][C:8]=3[C:15]3[S:16][CH:17]=[C:18]([C:20]([F:23])([F:22])[F:21])[N:19]=3)[CH:35]=2)[C:30](=[O:38])[C:29]([C:39]([O:41][CH2:42][CH3:43])=[O:40])=[CH:28]1)[CH3:26]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 19081741HCID 19081741, compound2×HCID 594161896-(3-Ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid2×

Product 1

HCID 59617693HCID 59617693, compoundYield 60%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

To a slurry of 6-(3-ethylureido)-4-(4-trifluoromethylthiazol-2-yl)pyridin-3-ylboronic acid (Intermediate 17, 330 mg, 0.91 mmol), ethyl 1-ethyl7-iodo-4-oxo-1,4-dihydroquinoline-3-carboxylate (Intermediate 9, 281 mg, 0.75 mmol) and trans-dichlorobis(triphenylphosphine)palladium (II) (53 mg, 0.075 mmol) in 1,4-dioxane (8 ml) was added a solution of potassium carbonate (210 mg, 1.52 mmol) in water (3 ml). The reaction was stirred for 1.5 hours at 70° C. The reaction was cooled to room temperature, and ethyl acetate (8 mL) was added to help separate the layers. The water was removed, and the organic phase was washed with water (3 mL). The reaction was then concentrated and ethanol (5 mL) was added. The suspension was filtered, and the solid washed with methyl tert-butyl ether (2×, 5 ml). The solid was dried in a vacuum oven at 50° C. for 4 hours to give 195 mg (60%) of ethyl 1-ethyl7-(6-(3-ethylureido)-4-(4-trifluoromethylthiazol-2-yl)pyridin-3-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate as an off white solid.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customto help separate the layers
  3. customThe water was removed
  4. washthe organic phase was washed with water (3 mL)
  5. concentrationThe reaction was then concentrated
  6. additionethanol (5 mL) was added
  7. filtrationThe suspension was filtered
  8. washthe solid washed with methyl tert-butyl ether (2×, 5 ml)
  9. customThe solid was dried in a vacuum oven at 50° C. for 4 hours

Sources & evidence

ORD record
ord-1a49620e20544981a0562ea96545cbd2
Source dataset
uspto-grants-2012_10
Patent number
US08283361B2

Reaction notes

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