Trifluoroacetic acid → HCID 71598532, compound

HRID 1396379Notes

Reaction equation

HRID 1396379 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:30](=[O:32])[NH2:31])=[C:19]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([CH2:28][CH3:29])[N: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:30]([NH2:31])=[O:32])=[C:19]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([CH2:28][CH3:29])[N:23]=2)[CH:20]=1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 86689740HCID 86689740, compound

Product 2

HCID 14923Ammonium HydroxideHCID 71598532HCID 71598532, compoundYield 101.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

{(1S,2R)-2-[6-Carbamoyl-5-(6-ethyl-pyridin-2-ylamino)-pyridazin-3-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester (167 mg, 0.367 mmol) was dissolved in dichloromethane (4 mL) then cooled to 0° C. Trifluoroacetic acid (2 mL, 26 mmol) was added drop-wise then the reaction mixture was warmed to 25° C. After 5 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, 5 to 80% of a 0.1:0.01 solution of methanol:NH4OH in dichloromethane) gave 6-((1R,2S)-2-amino-cyclohexylamino)-4-(6-ethyl-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide (66 mg, 50%) as a light brown solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.66 (s, 1H) 8.35-8.40 (m, 1H) 8.09 (s, 1H) 7.63 (dd, J=8.2, 7.5 Hz, 1H) 7.62 (br. s., 1H) 6.86 (d, J=7.6 Hz, 1H) 6.79 (d, J=7.6 Hz, 1H) 6.76 (d, J=7.8 Hz, 1H) 3.73-3.86 (m, 1H) 3.10-3.15 (m, 1H) 2.75 (q, J=7.6 Hz, 2H) 1.48-1.73 (m, 7H) 1.27 (t, J=7.7 Hz, 3H) 1.24-1.37 (m, 2H); LCMS (EI/CI) m/z: 356 [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, 5 to 80% of a 0.1:0.01 solution of methanol

Sources & evidence

ORD record
ord-5438af398fda43399c6ddfd7e231f8af
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

Loading…