trans-2-Aminomethyl-1-cyclohexanol → HCID 20788997, compound

HRID 1353687Notes

Reaction equation

HRID 1353687 reaction equation
C([N:4]1[C:12]2[C:7](=[CH:8][C:9]([C:13](Cl)=[O:14])=[CH:10][CH:11]=2)[C:6]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)=[N:5]1)(=O)C.[NH2:23][CH2:24][C@@H:25]1[CH2:30][CH2:29][CH2:28][CH2:27][C@H:26]1[OH:31]>N1C=CC=CC=1>[OH:31][C@@H:26]1[CH2:27][CH2:28][CH2:29][CH2:30][CH:25]1[CH2:24][NH:23][C:13]([C:9]1[CH:8]=[C:7]2[C:12](=[CH:11][CH:10]=1)[NH:4][N:5]=[C:6]2[C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=1)=[O:14]

Participants

4

Reactant 2

HCID 2724658trans-2-Aminomethyl-1-cyclohexanolHCID 224802271-acetyl-3-(4-fluorophenyl)-1H-indazole-5-carbonyl chloride

Product 1

HCID 20788997HCID 20788997, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
60 °C

Procedure

To a flask containing 1-acetyl-3-(4-fluorophenyl)-1H-indazole-5-carbonyl chloride (330 mg, 0.95 mmol) dissolved in pyridine (6 mL) was added trans-2-aminomethyl-1-cyclohexanol (135.6 mg, 1.05 mmol). The reaction was allowed to stir under a nitrogen atmosphere overnight. Solvent was removed and the reaction was extracted with ethyl acetate. The organic phase was washed with a saturated aqueous solution of sodium bicarbonate, dried with magnesium sulfate, filtered and concentrated to yield the crude product. The product was purified by column chromatography (SiO2, 5% methanol in dichloromethane). The compound was taken up in a 3% ammonia in methanol solution (8 mL) and allowed to reflux at 60° C. for three hours. The reaction was neutralized with 1 N HCl solution and extracted with ethyl acetate. The organic layer was dried with magnesium sulfate, filtered and concentrated to yield the title compound (240 mg, 69% yield). 1H NMR (DMSO-d6) δ 13.5 (s, 1H), 8.6 (s, 2H), 8.1 (m, 2H), 7.9 (d, 1H), 7.6 (d, 1H), 7.4 (m, 2H), 4.8 (s, 1H), 3.5 (m, 1H), 3.2 (m, 1H), 1.8 (m, 2H), 1.6 (m, 2H), 1.4 (m, 2H), 0.8–1.0 (m, 3H), ES-MS m/z 368 [M+1]+.

Workup

  1. customSolvent was removed
  2. extractionthe reaction was extracted with ethyl acetate
  3. washThe organic phase was washed with a saturated aqueous solution of sodium bicarbonate
  4. dry with materialdried with magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto yield the crude product
  8. customThe product was purified by column chromatography (SiO2, 5% methanol in dichloromethane)
  9. extractionextracted with ethyl acetate
  10. dry with materialThe organic layer was dried with magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-f9e0c04930a0445083f1d907a0b0362c
Source dataset
uspto-grants-2007_05
Patent number
US07220771B2

Reaction notes

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