Trifluoroacetic acid → HCID 71626099, compound

HRID 1396466Notes

Reaction equation

HRID 1396466 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]([C:32]([OH:35])([CH3:34])[CH3:33])[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]([C:32]([OH:35])([CH3:33])[CH3:34])[N:27]=2)[CH:6]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86689799HCID 86689799, compound

Product 1

HCID 71626099HCID 71626099, compoundYield 56.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6-(2-hydroxypropan-2-yl)pyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (179 mg, 369 μmol) in CH2Cl2 (3.00 mL) was added TFA (1.48 g, 1.00 mL, 13.0 mmol) and mixture stirred to room temperature for 18 h. The solvent was evaporated and the residue purified by flash chromatography (spherical silica 20-45 μM, 23 g, Versaflash Supelco) eluting with 0 to 5% over 20 min (MeOH containing 10% NH4OH)/CH2Cl2 to give 6-((1R,2S)-2-aminocyclohexylamino)-4-(6-(2-hydroxypropan-2-yl)pyridin-2-ylamino)pyridazine-3-carboxamide (80 mg, 56.3% yield) as an off-white foam. 1H NMR (DMSO-d6) δ: 11.76 (s, 1H), 8.38 (br. s., 1H), 7.90 (s, 1H), 7.60-7.78 (m, 2H), 7.23 (d, J=7.6 Hz, 1H), 6.70-6.83 (m, 2H), 5.18 (s, 1H), 3.70 (br. s., 1H), 3.09 (br. s., 1H), 1.21-1.77 (m, 16H); LC-MS 386.1 [M+H]+.

Workup

  1. customThe solvent was evaporated
  2. customthe residue purified by flash chromatography (spherical silica 20-45 μM, 23 g, Versaflash Supelco)
  3. washeluting with 0 to 5% over 20 min (MeOH containing 10% NH4OH)/CH2Cl2

Sources & evidence

ORD record
ord-7c861157a7a64d88bcb8f95e138037b7
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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