Potassium Carbonate → HCID 59415994, compound

HRID 2061835Notes

Reaction equation

HRID 2061835 reaction equation
[OH:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[N:8]1[C:17]2[C:12](=[CH:13][C:14](I)=[CH:15][CH:16]=2)[C:11](=[O:19])[C:10]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:9]1.[CH2:25]([NH:27][C:28]([NH:30][C:31]1[CH:36]=[C:35]([C:37]2[S:38][CH:39]=[C:40]([C:42]([F:45])([F:44])[F:43])[N:41]=2)[C:34](B2OC(C)(C)C(C)(C)O2)=[CH:33][N:32]=1)=[O:29])[CH3:26].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]>[CH2:25]([NH:27][C:28](=[O:29])[NH:30][C:31]1[N:32]=[CH:33][C:34]([C:14]2[CH:13]=[C:12]3[C:17](=[CH:16][CH:15]=2)[N:8]([C@@H:3]2[CH2:4][CH2:5][CH2:6][CH2:7][C@@H:2]2[OH:1])[CH:9]=[C:10]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[C:11]3=[O:19])=[C:35]([C:37]2[S:38][CH:39]=[C:40]([C:42]([F:45])([F:44])[F:43])[N:41]=2)[CH:36]=1)[CH3:26]

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 59416072HCID 59416072, compound2×

Product 1

HCID 59415994HCID 59415994, compoundYield 78.9%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 12976736Bis(ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane);iron(2+)CatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent2×

Conditions

Temperature
100 °C

Procedure

Palladium (II) acetate (0.027 g, 0.12 mmol) and 1,1′-bis(di-t-butylphosphino)ferrocene (0.058 g, 0.12 mmol) were dissolved in 1 ml of acetonitrile. Ethyl 1-(cis-2-hydroxycyclohexyl)-6-iodo-4-oxo-1,4-dihydroquinoline-3-carboxylate (Intermediate 121, 0.539 g, 1.22 mmol) and 6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid (Intermediate 17, 0.444 g, 1.23 mmol) were added along with an additional 2 ml of acetonitrile. Potassium carbonate (0.253 g, 1.83 mmol) was dissolved in water (1.333 mL) then added to the mixture. The reaction was stirred at 100° C. for 30 min, then cooled to room temperature and quenched with water (2 ml). The precipitate was filtered off and washed with water, ethyl acetate and hexanes, then dried in a vacuum oven at 50° C. for 18 h to give 0.606 g (78%) of ethyl 6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1-(cis-2-hydroxycyclohexyl)-4-oxo-1,4-dihydroquinoline-3-carboxylate as a light brown solid.

Workup

  1. additionthen added to the mixture
  2. temperaturecooled to room temperature
  3. customquenched with water (2 ml)
  4. filtrationThe precipitate was filtered off
  5. washwashed with water, ethyl acetate and hexanes
  6. customdried in a vacuum oven at 50° C. for 18 h

Sources & evidence

ORD record
ord-3665bad43e6945e79c85e3c524dd157e
Source dataset
uspto-grants-2012_10
Patent number
US08283361B2

Reaction notes

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