Lithium Hydroxide → HCID 22171106, compound

HRID 1823227Notes

Reaction equation

HRID 1823227 reaction equation
C([O:3][C:4](=[O:33])[CH:5]([C:26]1[CH:27]=[C:28]([CH3:32])[CH:29]=[CH:30][CH:31]=1)[CH2:6][C:7]1[CH:11]=[C:10]([C:12]2[CH:17]=[CH:16][C:15](Br)=[CH:14][CH:13]=2)[N:9]([C:19]2[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=2)[N:8]=1)C.C[NH:35][C@@H:36]1[CH2:41]CCC[C@H]1NC.C([O-])([O-])=[O:45].[K+].[K+].CNC=O.[Li+].[OH-]>O1CCOCC1.[Cu]I.C1COCC1.O>[C:36]([NH:35][C:15]1[CH:16]=[CH:17][C:12]([C:10]2[N:9]([C:19]3[CH:20]=[CH:21][C:22]([CH3:25])=[CH:23][CH:24]=3)[N:8]=[C:7]([CH2:6][CH:5]([C:26]3[CH:27]=[C:28]([CH3:32])[CH:29]=[CH:30][CH:31]=3)[C:4]([OH:3])=[O:33])[CH:11]=2)=[CH:13][CH:14]=1)(=[O:45])[CH3:41]

Participants

9

Reactant 5

HCID 3939Lithium HydroxideHCID 11430Potassium CarbonateHCID 31254N-MethylformamideHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 23568904HCID 23568904, compound

Product 1

HCID 22171106HCID 22171106, compoundYield 551.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolventHCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
110 °C

Procedure

To a solution of 3-[5-(4-bromo-phenyl)-1-p-tolyl-1H-pyrazol-3-yl]-2-m-tolyl-propionic acid ethyl ester (Example 77, Step C; 100 mg, 0.2 mmol) in dioxane (0.6 mL) was added CuI (3 mg, 0.02 mmol, 10 mol %), (1R,2R)-N,N′-dimethyl-cyclohexane-1,2-diamine (0.003 mL, 0.02 mmol, 10 mol %), K2CO3 (55 mg, 0.40 mmol, 2.0 equiv) and N-methylformamide (15 mg, 0.26 mmol, 1.3 equiv). The mixture was stirred at 110° C. for 14 h, and then cooled to 45° C. prior to the addition of a solution of LiOH (28 mg, 1.2 mmol, 3 equiv) in 2:1 THF/H2O (1 mL). After 3 h at 45° C., the reaction mixture was purified by preparative reversed-phase HPLC (acetonitrile/water) to afford the title compound (50 mg, 50%). HPLC: Rt=3.62 (Method A). MS (ESI): mass calculated for C28H27N3O3, 453.21; m/z found, 454.3 [M+H]+. 1H NMR (500 MHz, CDCl3): 7.43-7.39 (m, 3H), 7.25-7.17 (m, 3H), 7.10-7.06 (m, 6H), 6.24 (s, 1H), 4.09 (dd, J=10.0, 5.2 Hz, 1H), 3.53 (dd, J=15.0, 10.0 Hz, 1H), 3.13-3.09 (dd, J=15.0, 5.2 Hz, 1H), 2.34 (s, 6H), 2.16 (S, 3H).

Workup

  1. temperaturecooled to 45° C.
  2. waitAfter 3 h at 45° C.
  3. customthe reaction mixture was purified by preparative reversed-phase HPLC (acetonitrile/water)

Sources & evidence

ORD record
ord-cbbe6fdc898f4b76a426ddee10b4b67b
Source dataset
uspto-grants-2006_05
Patent number
US07037931B2

Reaction notes

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