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

HRID 1396373Notes

Reaction equation

HRID 1396373 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[CH2:34][CH2:33]2)[N:27]=1)(=[O:3])[NH2:2].C(O)(C(F)(F)F)=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]([CH:32]3[CH2:33][CH2:34]3)[N:27]=2)[CH:6]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86689734tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6-cyclopropylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate

Product 1

HCID 716268946-((1R,2S)-2-aminocyclohexylamino)-4-(6-cyclopropylpyridin-2-ylamino) pyridazine-3-carboxamideYield 66.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6-cyclopropylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (25 mg, 53.5 μmol) in dichloromethane (4 mL) was added TFA (370 μg, 0.25 μL, 3.24 μmol). After 6 h, the mixture was concentrated in vacuo, then purified by flash chromatography (spherical silica, 20-45 μm, 25 g, Versaflash from Supelco, 97:2.75:0.15 to 84:15.2:0.8 dichloromethane:MeOH:NH4OH, 30 min) to give 6-((1R,2S)-2-aminocyclohexylamino)-4-(6-cyclopropylpyridin-2-ylamino) pyridazine-3-carboxamide (13 mg, 10%, two steps) as a brown solid. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 11.43 (br. s., 1H) 8.17 (br. s., 1H) 8.03 (br. s., 1H) 7.44 (br. s., 1H) 7.03 (br. s., 1H) 6.80 (br. s., 1H) 6.60 (br. s., 1H) 5.76 (br. s., 1H) 5.49 (br. s., 1H) 3.82 (br. s., 1H) 3.24 (br. s., 1H) 2.03 (br. s., 1H) 1.32-1.91 (m, 8H) 1.05 (d, J=16.62 Hz, 4H). LCMS (EI/CI) m/z: 368 [M+H].

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. custompurified by flash chromatography (spherical silica, 20-45 μm, 25 g, Versaflash from Supelco, 97:2.75:0.15 to 84:15.2:0.8 dichloromethane:MeOH:NH4OH, 30 min)

Sources & evidence

ORD record
ord-cf9ea56ef0f444f1931c689838c8a9da
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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