Trifluoroacetic acid → 6-((1R,2S)-2-aminocyclohexylamino)-4-(6-ethoxypyridin-2-ylamino)pyridazine-3-carboxamide

HRID 1396432Notes

Reaction equation

HRID 1396432 reaction equation
[C:1]([C:4]1[N:9]=[N:8][C:7]([NH:10][C@@H:11]2[CH2:16][CH2:15][CH2:14][CH2:13][C@@H:12]2[NH:17]C(=O)OC(C)(C)C)=[CH:6][C:5]=1[NH:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([O:32][CH2:33][CH3:34])[N:27]=1)(=[O:3])[NH2:2].FC(F)(F)C(O)=O>ClCCl>[NH2:17][C@H:12]1[CH2:13][CH2:14][CH2:15][CH2:16][C@H:11]1[NH:10][C:7]1[N:8]=[N:9][C:4]([C:1]([NH2:2])=[O:3])=[C:5]([NH:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([O:32][CH2:33][CH3:34])[N:27]=2)[CH:6]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86689776tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6-ethoxypyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate

Product 1

HCID 716260406-((1R,2S)-2-aminocyclohexylamino)-4-(6-ethoxypyridin-2-ylamino)pyridazine-3-carboxamideYield 66%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

tert-Butyl (1S,2R)-2-(6-carbamoyl-5-(6-ethoxypyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (32.2 mg, 51.2 μmol) was dissolved in dichloromethane (1 mL) and treated with trifluoroacetic acid (744 mg, 0.5 mL, 6.53 mmol). The reaction was stirred at 25° C. for 3 h then concentrated in vacuo to a brown oil. This oil was dissolved in dichloromethane, washed with 1N NaOH (3×5 mL) and brine (5 mL), then the organic phase was dried (Na2SO4), filtered and concentrated to give an off-white solid. The solid was triturated with Et2O (3×5 mL) and dried overnight in vacuo to give an off-white solid, 6-((1R,2S)-2-aminocyclohexylamino)-4-(6-ethoxypyridin-2-ylamino)pyridazine-3-carboxamide (12.6 mg, 33.6 μmol, 66% yield), 1H NMR (DMSO-d6) δ: 11.65 (br. s., 1H), 8.40 (br. s., 1H), 7.71 (s, 1H), 7.64 (t, J=7.9 Hz, 2H), 6.77 (d, J=7.8 Hz, 1H), 6.54 (d, J=7.8 Hz, 1H), 6.36-6.42 (m, 1H), 4.35 (q, J=7.0 Hz, 2H), 3.85 (br. s., 1H), 3.09 (br. s., 1H), 1.48-1.74 (m, 6H), 1.20-1.40 (m, 5H); MS (EI/CI) m/z: 372.3 [M+H].

Workup

  1. concentrationthen concentrated in vacuo to a brown oil
  2. dissolutionThis oil was dissolved in dichloromethane
  3. washwashed with 1N NaOH (3×5 mL) and brine (5 mL)
  4. dry with materialthe organic phase was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give an off-white solid
  8. customThe solid was triturated with Et2O (3×5 mL)
  9. customdried overnight in vacuo

Sources & evidence

ORD record
ord-ea61ff223abe44fb8bfdcb70b48e1699
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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