Lithium Hydroxide → HCID 59415945, compound

HRID 2061834Notes

Reaction equation

HRID 2061834 reaction equation
I[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:12][C@@H:13]1[CH2:18][CH2:17][CH2:16][NH:15][CH2:14]1)[CH:7]=[C:6]([C:19]([O:21]CC)=[O:20])[C:5]2=[O:24].[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-].[Cs+].[Cs+].[OH-].[Li+]>O1CCOCC1.O.C1C=CC([P]([Pd]([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)=CC=1>[CH2:25]([NH:27][C:28](=[O:29])[NH:30][C:31]1[N:32]=[CH:33][C:34]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]([CH2:12][C@@H:13]2[CH2:18][CH2:17][CH2:16][NH:15][CH2:14]2)[CH:7]=[C:6]([C:19]([OH:21])=[O:20])[C:5]3=[O:24])=[C:35]([C:37]2[S:38][CH:39]=[C:40]([C:42]([F:43])([F:44])[F:45])[N:41]=2)[CH:36]=1)[CH3:26]

Participants

8

Reactant 4

HCID 3939Lithium HydroxideHCID 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 59415796(R)-ethyl 6-iodo-4-oxo-1-(piperidin-3-ylmethyl)-1,4-dihydroquinoline-3-carboxylate2×

Product 1

HCID 59415945HCID 59415945, compoundYield 36.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (R)-ethyl 6-iodo-4-oxo-1-(piperidin-3-ylmethyl)-1,4-dihydroquinoline-3-carboxylate (Intermediate 108, 200 mg, 0.42 mmol, 1 equiv.) and 6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid (Intermediate 17, 151 mg, 0.42 mmol, 1 equiv.) in 1,4-dioxane (4.5 mL) was added tetrakis(triphenylphosphine)palladium(0) (48.5 mg, 0.04 mmol, 0.1 equiv.) followed by a solution of cesium carbonate (205 mg, 0.63 mmol, 1.5 equiv.) in water (1.5 mL). This was stirred at 100° C. for 2 h. 2 M lithium hydroxide (0.629 mL, 1.26 mmol, 3 equiv.) was then added and the mixture was stirred at 100° C. for 12 h. The reaction mixture was diluted with water, and the precipitate that formed was collected by filtration, washed with water and hexanes and dried under vacuum. Purification via reverse phase HPLC (C18, 0-95% acteonitirile/water gradient) gave (R)-6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-4-oxo-1-(piperidin-3-ylmethyl)-1,4-dihydroquinoline-3-carboxylic acid as a light yellow solid (92.5 mg, 36%).

Workup

  1. stirringthe mixture was stirred at 100° C. for 12 h
  2. customthe precipitate that formed
  3. filtrationwas collected by filtration
  4. washwashed with water and hexanes
  5. customdried under vacuum
  6. customPurification via reverse phase HPLC (C18, 0-95% acteonitirile/water gradient)

Sources & evidence

ORD record
ord-04bcd7d247b64bf090daa43782a812e6
Source dataset
uspto-grants-2012_10
Patent number
US08283361B2

Reaction notes

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