Potassium Carbonate → HCID 44540075, compound

HRID 2061810Notes

Reaction equation

HRID 2061810 reaction equation
[OH:1][CH2:2][C@@H:3]([N:11]1[C:20]2[C:15](=[CH:16][C:17](I)=[CH:18][CH:19]=2)[C:14](=[O:22])[C:13]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:12]1)[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[CH2:28]([NH:30][C:31]([NH:33][C:34]1[CH:39]=[C:38]([C:40]2[S:41][CH:42]=[C:43]([C:45]([F:48])([F:47])[F:46])[N:44]=2)[C:37](B2OC(C)(C)C(C)(C)O2)=[CH:36][N:35]=1)=[O:32])[CH3:29].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]>[CH2:28]([NH:30][C:31](=[O:32])[NH:33][C:34]1[N:35]=[CH:36][C:37]([C:17]2[CH:16]=[C:15]3[C:20](=[CH:19][CH:18]=2)[N:11]([C@@H:3]([CH2:4][C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH2:2][OH:1])[CH:12]=[C:13]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:14]3=[O:22])=[C:38]([C:40]2[S:41][CH:42]=[C:43]([C:45]([F:48])([F:47])[F:46])[N:44]=2)[CH:39]=1)[CH3:29]

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 59415923HCID 59415923, compound2×

Product 1

HCID 44540075HCID 44540075, compoundYield 89%

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 (23.52 mg, 0.10 mmol, 0.1 equiv.) and 1,1′-bis(di-t-butylphosphino)ferrocene (49.7 mg, 0.10 mmol, 0.1 equiv.) in acetonitrile (3 mL) was added (S)-ethyl 1-(1-hydroxy-3-phenylpropan-2-yl)-6-iodo-4-oxo-1,4-dihydroquinoline-3-carboxylate (Intermediate 51, 500 mg, 1.05 mmol), followed by 6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazole-2-yl)pyridine-3-ylboronic acid (Intermediate 17, 381 mg, 1.06 mmol) and a solution of potassium carbonate (217 mg, 1.57 mmol) 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 reaction mixture was partitioned between water (10 mL) and ethyl acetate (10 mL). The aqueous layer was extracted with ethyl acetate (2×10 mL), and the organics were dried over sodium sulfate and concentrated to provide (S)-ethyl 6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1-(1-hydroxy-3-phenylpropan-2-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate as a grey solid (619 mg, 89%).

Workup

  1. temperaturecooled to room temperature
  2. customThe reaction mixture was partitioned between water (10 mL) and ethyl acetate (10 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (2×10 mL)
  4. dry with materialthe organics were dried over sodium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-3ada84853d1f421f9098978679029d95
Source dataset
uspto-grants-2012_10
Patent number
US08283361B2

Reaction notes

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