Trifluoroacetic acid → HCID 71626970, compound

HRID 1396404Notes

Reaction equation

HRID 1396404 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]([CH:32]2[CH2:35][CH2:34][CH2:33]2)[N:27]=1)(=[O:3])[NH2:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[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]([CH:32]3[CH2:33][CH2:34][CH2:35]3)[N:27]=2)[CH:6]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86689756HCID 86689756, compound

Product 1

HCID 71626970HCID 71626970, compoundYield 54.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a 25 mL round bottom flask, a solution of tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6-cyclobutylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (112 mg, 233 μmol) in CH2Cl2 (5.0 mL) was treated with TFA (2.22 g, 1.5 mL, 19.5 mmol) and the mixture stirred to room temperature for 18 h. Solvents evaporated and residue purified by flash chromatography (spherical silica 20-45 μM, 80 g, Versaflash Supelco) eluting with 0 to 10% over 30 min (MeOH containing 10% NH4OH)/CH2Cl2 to give 6-((1R,2S)-2-aminocyclohexylamino)-4-(6-cyclobutylpyridin-2-ylamino)pyridazine-3-carboxamide (48 mg, 126 μmol, 54.1% yield) as an off-white solid. 1H NMR (CHLOROFORM-d) δ: 11.43 (br. s., 1H), 8.45 (s, 1H), 8.03 (br. s., 1H), 7.51 (t, J=7.7 Hz, 1H), 6.75 (d, J=7.2 Hz, 1H), 6.68 (d, J=7.9 Hz, 1H), 5.62 (d, J=8.3 Hz, 1H), 5.37 (br. s., 1H), 3.88 (br. s., 1H), 3.65 (quin, J=8.5 Hz, 1H), 3.22 (d, J=4.9 Hz, 1H), 2.27-2.51 (m, 4H), 1.99-2.22 (m, 1H), 1.94 (dd, J=11.1, 5.5 Hz, 1H), 1.07-1.84 (m, 10H); LC-MS 382.0 [M+H]+.

Workup

  1. customSolvents evaporated
  2. customresidue purified by flash chromatography (spherical silica 20-45 μM, 80 g, Versaflash Supelco)
  3. washeluting with 0 to 10% over 30 min (MeOH containing 10% NH4OH)/CH2Cl2

Sources & evidence

ORD record
ord-37a04d3285024a78b53d4bb0f410920e
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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