Trifluoroacetic acid → HCID 71625974, compound

HRID 1396427Notes

Reaction equation

HRID 1396427 reaction equation
[C:1]([C:5]1[N:10]=[C:9]([NH:11][C:12]2[CH:13]=[C:14]([NH:21][C@@H:22]3[CH2:27][CH2:26][O:25][CH2:24][C@@H:23]3[NH:28]C(=O)OC(C)(C)C)[N:15]=[N:16][C:17]=2[C:18](=[O:20])[NH2:19])[CH:8]=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:28][C@@H:23]1[C@H:22]([NH:21][C:14]2[N:15]=[N:16][C:17]([C:18]([NH2:19])=[O:20])=[C:12]([NH:11][C:9]3[CH:8]=[CH:7][CH:6]=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[N:10]=3)[CH:13]=2)[CH2:27][CH2:26][O:25][CH2:24]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86689773HCID 86689773, compound

Product 1

HCID 71625974HCID 71625974, compoundYield 40.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl (3R,4R)-4-(5-(6-tert-butylpyridin-2-ylamino)-6-carbamoylpyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate (73 mg, 150 μmol) in CH2Cl2 (3.00 mL) was added TFA (1.48 g, 1 mL, 13.0 mmol) and the 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-((3R,4R)-3-aminotetrahydro-2H-pyran-4-ylamino)-4-(6-tert-butylpyridin-2-ylamino)pyridazine-3-carboxamide (23.5 mg, 40.5% yield) as an off-white solid. 1H NMR (CHLOROFORM-d) δ: 11.45 (s, 1H), 8.38 (s, 1H), 8.03 (br. s., 1H), 7.54 (t, J=7.9 Hz, 1H), 6.93 (d, J=7.6 Hz, 1H), 6.69 (d, J=7.9 Hz, 1H), 5.83 (d, J=8.3 Hz, 1H), 5.37 (br. s., 1H), 3.91-4.13 (m, 2H), 3.86 (d, J=11.0 Hz, 1H), 3.65 (d, J=10.6 Hz, 1H), 3.41-3.58 (m, 1H), 3.04 (br. s., 1H), 1.97 (d, J=9.4 Hz, 1H), 1.63-1.85 (m, 1H), 1.55 (br. s., 3H), 1.42 (s, 9H); LC-MS 386.2 [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-f7d891bb1ea24f2c99052111905099aa
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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