Ethanol → HCID 67271746, compound

HRID 1696578Notes

Reaction equation

HRID 1696578 reaction equation
CCO.O.[CH:5]1([C:10]2[CH:14]=[C:13]([NH:15][C:16]([NH:18][C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[C:20]=3[Cl:26])=[O:17])[N:12]([C:27]3[CH:35]=[C:34]4[C:30]([CH2:31][CH2:32][CH:33]4[C:36]([O:38]CC)=[O:37])=[CH:29][CH:28]=3)[N:11]=2)[CH2:9][CH2:8][CH2:7][CH2:6]1.[OH-].[Li+]>C(O)(=O)CC(CC(O)=O)(C(O)=O)O.C(OCC)(=O)C.O1CCOCC1>[CH:5]1([C:10]2[CH:14]=[C:13]([NH:15][C:16]([NH:18][C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[C:20]=3[Cl:26])=[O:17])[N:12]([C:27]3[CH:35]=[C:34]4[C:30]([CH2:31][CH2:32][CH:33]4[C:36]([OH:38])=[O:37])=[CH:29][CH:28]=3)[N:11]=2)[CH2:6][CH2:7][CH2:8][CH2:9]1

Participants

8

Reactant 4

HCID 702EthanolHCID 962WaterHCID 3939Lithium HydroxideHCID 67271721HCID 67271721, compound

Product 1

HCID 67271746HCID 67271746, compound

Reagents, catalysts & solvents 3

HCID 311Citric AcidSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

In a 1:1:1 mix of EtOH:H2O:dioxane (6 mL) was placed ethyl 6-(3-cyclopentyl-5-(3-(2,3-dichlorophenyl)ureido)-1H-pyrazol-1-yl)-2,3-dihydro-1H-indene-1-carboxylate (520 mg, 0.986 mmol) and lithium hydroxide (71 mg, 2.96 mmol). The solution warmed to 40 C and stirred, ON. LC shows complete reaction. The solution cooled to RT and diluted with 5% citric acid (20 mL) and Ethyl acetate (20 mL). The organic phase separated, washed with brine and dried over sodium sulfate. The solvents were evaporated at reduced pressure to give 6-(3-cyclopentyl-5-(3-(2,3-dichlorophenyl)ureido)-1H-pyrazol-1-yl)-2,3-dihydro-1H-indene-1-carboxylic acid as a foam, 474 mg (96%), used as is. In DMF (5 mL) was placed 6-(3-cyclopentyl-5-(3-(2,3-dichlorophenyl)ureido)-1H-pyrazol-1-yl)-2,3-dihydro-1H-indene-1-carboxylic acid (474 mg, 0.949 mmol), HOBt (196 mg, 1.09 mmol) and EDAC (218 mg, 1.42 mmol). The mixture was stirred at RT for 1 hr and then treated with a solution of 0.5N ammonia in dioxane (7.59 mL, 3.80 mmol). The mixture was stirred at RT, ON. LC shows complete reaction. The mixture was diluted with 5% citric acid (20 mL) and Ethyl acetate (20 mL). The organic phase separated, washed with saturated sodium bicarbonate (20 mL), brine (20 mL) and dried over sodium sulfate. The solvents evaporated at reduced pressure to give a foam, dried on high vacuum line at RT for 2 hrs. The foam was then purified by Biotage chromatography (S1-25 column, 65-95% Ethyl acetate/Hex). Fractions 10-19 were combined and evaporated at reduced pressure to give 1-(1-(3-carbamoyl-2,3-dihydro-1H-inden-5-yl)-3-cyclopentyl-1H-pyrazol-5-yl)-3-(2,3-dichlorophenyl)urea as a white solid. The solid was dried on the high vacuum line at 65 C in the abderhalden for 3 hrs, 210 mg (44%). 1H NMR (DMSO-d6) 1.59-1.73 (m, 6H), 1.95-1.99 (m, 2H), 2.23-2.33 (m, 2H), 2.88-3.06 (m, 3H), 3.90-4.04 (m, 1H), 6.31 (s, 1H), 6.98 (s, 1H), 7.26-7.42 (m, 5H), 7.63 (br s, 1H), 8.07-8.09 (m, 1H), 8.77 (s, 1H), 9.21 (s, 1H). LC-MS (EI) m/z: 500.0 (M+H+).

Workup

  1. temperatureThe solution warmed to 40 C
  2. customreaction
  3. customThe organic phase separated
  4. washwashed with brine
  5. dry with materialdried over sodium sulfate
  6. customThe solvents were evaporated at reduced pressure

Sources & evidence

ORD record
ord-7a0ab35472ca4f618234ca9cc0178fa1
Source dataset
uspto-grants-2012_04
Patent number
US08163756B2

Reaction notes

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