Salicylaldehyde oxime → HCID 42610076, compound

HRID 474156Notes

Reaction equation

HRID 474156 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:11][C@@H:12]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][CH2:21][C:22]([F:25])([F:24])[F:23])=[CH:16][N:15]=2)[CH3:13])=[O:10])=[CH:4][CH:3]=1.[CH:26]1([C:29]2[C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[NH:31][N:30]=2)[CH2:28][CH2:27]1.C(=O)([O-])[O-].[Cs+].[Cs+].C(=NO)C1C(=CC=CC=1)O>[Cu-]=O.O.CC#N>[CH:26]1([C:29]2[C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[N:31]([C:2]3[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:11][C@@H:12]([C:14]4[CH:19]=[CH:18][C:17]([NH:20][CH2:21][C:22]([F:25])([F:24])[F:23])=[CH:16][N:15]=4)[CH3:13])=[O:10])=[CH:4][CH:3]=3)[N:30]=2)[CH2:28][CH2:27]1

Participants

8

Reactant 4

HCID 7200Salicylaldehyde oximeHCID 10796Cesium carbonateHCID 68496668HCID 68496668, compoundHCID 178419916HCID 178419916, compound

Product 1

HCID 42610076HCID 42610076, compoundYield 68%

Reagents, catalysts & solvents 3

HCID 178419072HCID 178419072, compoundCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
150 °C

Procedure

The starting 2-(4-iodophenyl)-N-((1R)-1-{5-[(2,2,2-trifluoroethyl)amino]pyridin-2-yl}ethyl)acetamide (130 mg, 0.280 mmol), 3-cyclopropyl-1H-indazole (66.5 mg, 0.420 mmol), copper (I) oxide (2.004 mg, 0.014 mmol), cesium carbonate (146 mg, 0.448 mmol), and salicylaldoxime (7.68 mg, 0.056 mmol) were mixed into 1.0 ml of CH3CN in a sealed bottle. The mixture was stirred at 150° C. overnight. After cooled, water (25 mL) was added and the mixture. Organics were extracted with CH2Cl2, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (gradient, 30-100% EtOAc in hexanes) to give 2-[4-(3-cyclopropyl-1H-indazole-1-yl)phenyl]-N-((1R)-1-{5-[(2,2,2-trifluoroethyl)amino]pyridin-2-yl}ethyl)acetamide as a light yellow solid (94 mg, 68%). 1H NMR (CDCl3, 400 MHz) δ 8.206 (d, J=2.57 Hz, 1H); 7.816 (d, J=8.06 Hz, 1H); 7.683 (m, 3H); 7.407 (m, 3H); 7.208 (m, 3H); 6.726 (d, J=7.14 Hz, 1H); 5.128 (quintet, J=6.96 Hz, 1H); 4.361 (dd, J=15.93, 7.96 Hz, 2H); 3.645 (s, 2H); 2.288 (m, 1H); 1.413 (d, J=6.77 Hz, 3H); 1.175 (m, 2H); 1.085 (m, 2H); MS (ES): m/z 495.2 (M+H). FLIPR alpha1I IP=73 nM.

Workup

  1. temperatureAfter cooled
  2. extractionOrganics were extracted with CH2Cl2
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel chromatography (gradient, 30-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-2a5bbcd3556d4cf5af814befd9ae2a07
Source dataset
uspto-grants-2014_01
Patent number
US08637513B2

Reaction notes

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