Trifluoroacetic acid → HCID 71626820, compound

HRID 1396345Notes

Reaction equation

HRID 1396345 reaction equation
C([O:5]C(=O)[NH:7][C@H:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]1[NH:14][C:15]1[N:16]=[N:17][C:18]([C:29](=[O:31])[NH2:30])=[C:19]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=2)[CH:20]=1)(C)(C)C.FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+]>ClCCl>[NH4+:7].[OH-:5].[NH2:7][C@H:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]1[NH:14][C:15]1[N:16]=[N:17][C:18]([C:29]([NH2:30])=[O:31])=[C:19]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=2)[CH:20]=1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 86689714[(1S,2R)-2-(6-carbamoyl-5-p-tolylamino-pyridazin-3-ylamino)-cyclohexyl]-carbamic acid tert-butyl ester

Product 2

HCID 14923Ammonium HydroxideHCID 71626820HCID 71626820, compoundYield 149.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

[(1S,2R)-2-(6-carbamoyl-5-p-tolylamino-pyridazin-3-ylamino)-cyclohexyl]-carbamic acid tert-butyl ester (26 mg, 0.059 mmol) was dissolved in dichloromethane (0.6 mL) then cooled to 0° C. Trifluoroacetic acid (0.27 mL, 3.54 mmol) was added drop-wise then the reaction mixture was warmed to 25° C. After 4 h, the mixture was cooled in an ice bath and neutralized with sodium bicarbonate solution. The mixture was extracted with ethyl acetate, and the combined organic layers washed with brine, dried (sodium sulfate), filtered, and concentrated in vacuo. Purification by chromatography (silica, 0 to 80% of a 0.1:0.01 solution of methanol:NH4OH in dichloromethane) gave 6-((1R,2S)-2-amino-cyclohexylamino)-4-p-tolylamino-pyridazine-3-carboxylic acid amide (15 mg, 72%) as an off-white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 10.30 (s, 1H) 8.20-8.30 (m, 1H) 7.44-7.55 (m, 1H) 7.17-7.27 (m, 2H) 7.07-7.17 (m, 2H) 6.59 (d, J=7.9 Hz, 1H) 6.33 (s, 1H) 3.95-4.09 (m, 1H) 2.93-3.06 (m, 1H) 2.30 (s, 3H) 1.19-1.68 (m, 9H); LCMS (EI/CI) m/z: 341 [M+H].

Workup

  1. temperaturethe reaction mixture was warmed to 25° C
  2. temperaturethe mixture was cooled in an ice bath
  3. extractionThe mixture was extracted with ethyl acetate
  4. washthe combined organic layers washed with brine
  5. dry with materialdried (sodium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by chromatography (silica, 0 to 80% of a 0.1:0.01 solution of methanol

Sources & evidence

ORD record
ord-8bb89752b4fb4315859cf914628c6a56
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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