Cesium carbonate → HCID 59416070, compound

HRID 2061811Notes

Reaction equation

HRID 2061811 reaction equation
[OH:1][CH2:2][CH:3]([N:6]1[C:15]2[C:10](=[CH:11][C:12](I)=[CH:13][CH:14]=2)[C:9](=[O:17])[C:8]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:7]1)[CH2:4][CH3:5].[CH2:23]([NH:25][C:26]([NH:28][C:29]1[CH:34]=[C:33]([C:35]2[S:36][CH:37]=[C:38]([C:40]([F:43])([F:42])[F:41])[N:39]=2)[C:32](B2OC(C)(C)C(C)(C)O2)=[CH:31][N:30]=1)=[O:27])[CH3:24].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.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>[CH2:23]([NH:25][C:26](=[O:27])[NH:28][C:29]1[N:30]=[CH:31][C:32]([C:12]2[CH:11]=[C:10]3[C:15](=[CH:14][CH:13]=2)[N:6]([CH:3]([CH2:4][CH3:5])[CH2:2][OH:1])[CH:7]=[C:8]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[C:9]3=[O:17])=[C:33]([C:35]2[S:36][CH:37]=[C:38]([C:40]([F:43])([F:42])[F:41])[N:39]=2)[CH:34]=1)[CH3:24]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 592084681-Ethyl-3-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-2-yl)urea2×HCID 59415991HCID 59415991, compound2×

Product 1

HCID 59416070HCID 59416070, compoundYield 28.9%

Reagents, catalysts & solvents 3

HCID 178420553HCID 178420553, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of ethyl 1-(1-hydroxybutan-2-yl)-6-iodo-4-oxo-1,4-dihydroquinoline-3-carboxylate (Intermediate 64, 282 mg, 0.78 mmol) and 6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazole-2-yl)pyridine-3-ylboronic acid (Intermediate 17, 350 mg, 0.84 mmol) in 1,4-dioxane (3 mL) was added a solution of cesium carbonate (467 mg, 1.43 mmol) in water (1 mL) followed by tetrakis(triphenylphosphino)palladium(0) (48.7 mg, 0.04 mmol). The reaction mixture was stirred at 100° C. for 2 h, cooled to room temperature, and diluted with water (2 mL). The precipitate that formed was collected by filtration, washed with water and hexanes. Purification via column chromatography (silica, 95:5 methylene chloride/methanol) provided ethyl 6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1-(1-hydroxybutan-2-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate as a yellow/orange solid (136 mg, 27%).

Workup

  1. temperaturecooled to room temperature
  2. customThe precipitate that formed
  3. filtrationwas collected by filtration
  4. washwashed with water and hexanes
  5. customPurification via column chromatography (silica, 95:5 methylene chloride/methanol)

Sources & evidence

ORD record
ord-82ed3ee33cab441fa99e08ed8d0cefbf
Source dataset
uspto-grants-2012_10
Patent number
US08283361B2

Reaction notes

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