Potassium Carbonate → (S)-ethyl 6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1-(1-hydroxypropan-2-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate

HRID 2061809Notes

Reaction equation

HRID 2061809 reaction equation
[OH:1][CH2:2][C@@H:3]([N:5]1[C:14]2[C:9](=[CH:10][C:11](I)=[CH:12][CH:13]=2)[C:8](=[O:16])[C:7]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:6]1)[CH3:4].[CH2:22]([NH:24][C:25]([NH:27][C:28]1[CH:33]=[C:32]([C:34]2[S:35][CH:36]=[C:37]([C:39]([F:42])([F:41])[F:40])[N:38]=2)[C:31](B2OC(C)(C)C(C)(C)O2)=[CH:30][N:29]=1)=[O:26])[CH3:23].C(=O)([O-])[O-].[K+].[K+]>C(#N)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2]>[CH2:22]([NH:24][C:25](=[O:26])[NH:27][C:28]1[N:29]=[CH:30][C:31]([C:11]2[CH:10]=[C:9]3[C:14](=[CH:13][CH:12]=2)[N:5]([C@@H:3]([CH3:4])[CH2:2][OH:1])[CH:6]=[C:7]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:8]3=[O:16])=[C:32]([C:34]2[S:35][CH:36]=[C:37]([C:39]([F:42])([F:41])[F:40])[N:38]=2)[CH:33]=1)[CH3:23]

Participants

8

Reactant 3

HCID 11430Potassium 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 59415847(S)-ethyl 1-(1-hydroxypropan-2-yl)-6-iodo-4-oxo-1,4-dihydroquinoline-3-carboxylate2×

Product 1

HCID 59416119(S)-ethyl 6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1-(1-hydroxypropan-2-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylateYield 79.1%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 12976736Bis(ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane);iron(2+)CatalystHCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of palladium (II) acetate (28.0 mg, 0.12 mmol, 0.1 equiv.) and 1,1′-bis(di-t-butylphosphino)ferrocene (59.1 mg, 0.12 mmol, 0.1 equiv.) in acetonitrile (3 mL) was added (S)-ethyl 1-(1-hydroxypropan-2-yl)-6-iodo-4-oxo-1,4-dihydroquinoline-3-carboxylate (Intermediate 49, 500 mg, 1.25 mmol), followed by 6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazole-2-yl)pyridine-3-ylboronic acid (Intermediate 17, 453 mg, 1.26 mmol) and a solution of potassium carbonate (258 mg, 1.87 mmol, 1.5 equiv.) in water (1 mL). The reaction mixture was stirred at 60° 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 and dried to provide (S)-ethyl 6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1-(1-hydroxypropan-2-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate as a grey solid (583 mg, 79%).

Workup

  1. temperaturecooled to room temperature
  2. customThe precipitate that formed
  3. filtrationwas collected by filtration
  4. washwashed with water and hexanes
  5. customdried

Sources & evidence

ORD record
ord-acb901397fc84879b92201ecd9855d86
Source dataset
uspto-grants-2012_10
Patent number
US08283361B2

Reaction notes

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