Trifluoroacetic acid → HCID 71626971, compound

HRID 1396416Notes

Reaction equation

HRID 1396416 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[N:31]=[C:30]2[CH2:32][CH2:33][CH2:34][C:29]2=[CH:28][CH:27]=1)(=[O:3])[NH2:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH4+:2].[OH-:3].[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[N:31]=[C:30]3[CH2:32][CH2:33][CH2:34][C:29]3=[CH:28][CH:27]=2)[CH:6]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86689765tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6,7-dihydro-5H-cyclopenta[b]pyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate

Product 2

HCID 14923Ammonium HydroxideHCID 71626971HCID 71626971, compoundYield 45.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6,7-dihydro-5H-cyclopenta[b]pyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (444 mg, 950 μmol) in CH2Cl2 (5 mL) was treated with TFA (4.08 g, 2.76 mL, 35.8 mmol) and the mixture stirred at room temperature for 18 h. The solvents were evaporated and the residue purified by flash chromatography (spherical silica 20-45 μM, 80 g, Versaflash Supelco) eluting with 0 to 5% of a 9:1 MeOH:NH4OH solution in CH2Cl2, 15 min) to give 6-((1R,2S)-2-aminocyclohexylamino)-4-(6,7-dihydro-5H-cyclopenta[b]pyridin-2-ylamino)pyridazine-3-carboxamide (80 mg, 23%) as an off-white solid. 1H NMR (DMSO-d6) δ: 11.54 (br. s., 1H), 8.35 (br. s., 1H), 7.95 (br. s., 1H), 7.46-7.69 (m, 2H), 6.80 (d, J=7.2 Hz, 1H), 6.69 (d, J=7.6 Hz, 1H), 3.89 (br. s., 1H), 3.12 (br. s., 1H), 2.75-2.98 (m, 4H), 1.96-2.17 (m, 2H), 1.61 (d, J=11.7 Hz, 8H), 1.31 (br. s., 2H); LC-MS 368.3 [M+H]+.

Workup

  1. customThe solvents were evaporated
  2. customthe residue purified by flash chromatography (spherical silica 20-45 μM, 80 g, Versaflash Supelco)
  3. washeluting with 0 to 5% of a 9:1 MeOH

Sources & evidence

ORD record
ord-27d64cf739704178bd4da88ce20bdab5
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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