Trifluoroacetic acid → HCID 71626972, compound

HRID 1396408Notes

Reaction equation

HRID 1396408 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[C:34]2[N:33]=[CH:32][N:31]([CH3:35])[C:30]=2[CH:29]=[CH:28][CH: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[C:34]3[N:33]=[CH:32][N:31]([CH3:35])[C:30]=3[CH:29]=[CH:28][CH:27]=2)[CH:6]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86689759HCID 86689759, compound

Product 1

HCID 71626972HCID 71626972, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl (1S,2R)-2-(6-carbamoyl-5-(1-methyl-1H-benzo[d]imidazol-4-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (132 mg, 275 μmol) in CH2Cl2 (5 mL) was treated with TFA (4.08 g, 2.76 mL, 35.8 mmol) and the reaction mixture stirred to room temperature for 18 h. The solvent was evaporated and the residue purified by chromatography (spherical silica 20-45 μM, 80 g, Versaflash Supelco, 0 to 10% of a 9:1 MeOH:NH4OH solution in CH2Cl2, 30 min) to give 6-((1R,2S)-2-aminocyclohexylamino)-4-(1-methyl-1H-benzo[d]imidazol-4-ylamino)pyridazine-3-carboxamide (70 mg, 67%) as an off-white solid. 1H NMR (DMSO-d6) δ: 11.06 (s, 1H), 8.23 (br. s., 1H), 8.16 (s, 1H), 7.50 (br. s., 1H), 7.15-7.37 (m, 3H), 6.75 (s, 1H), 6.70 (d, J=7.6 Hz, 1H), 4.09 (br. s., 1H), 3.84 (s, 3H), 3.08 (br. s., 1H), 1.54 (br. s., 6H), 1.26 (d, J=17.0 Hz, 2H); LC-MS 381.1 [M+H]+.

Workup

  1. customThe solvent was evaporated
  2. customthe residue purified by chromatography (spherical silica 20-45 μM, 80 g, Versaflash Supelco, 0 to 10% of a 9:1 MeOH:NH4OH solution in CH2Cl2, 30 min)

Sources & evidence

ORD record
ord-6b10a223145540378e0388baa77f1cc6
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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