Trifluoroacetic acid → HCID 71626045, compound

HRID 1396460Notes

Reaction equation

HRID 1396460 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]([C:35]#[N:36])([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]([C:35]#[N:36])([CH3:34])[CH3:33])[N:27]=2)[CH:6]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86689795HCID 86689795, compound

Product 1

HCID 71626045HCID 71626045, compoundYield 57.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6-(2-cyanopropan-2-yl)pyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (110 mg, 222 μmol) in CH2Cl2 (3.00 mL) was added TFA (1.48 g, 1.00 mL, 13.0 mmol) and the reaction mixture stirred to room temperature for 18 h. Solvents evaporated and residue purified by flash column (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-cyanopropan-2-yl)pyridin-2-ylamino)pyridazine-3-carboxamide (50 mg, 57% yield) as an off-white solid. 1H NMR (CHLOROFORM-d) δ: 11.47 (s, 1H), 8.76 (s, 1H), 8.06 (d, J=3.0 Hz, 1H), 7.60 (t, J=7.9 Hz, 1H), 6.86 (d, J=7.6 Hz, 1H), 6.78 (d, J=7.9 Hz, 1H), 5.60-5.77 (m, 2H), 4.25 (br. s., 1H), 3.11-3.24 (m, 1H), 1.32-1.92 (m, 16H); LC-MS 395.1 [M+H]+.

Workup

  1. customSolvents evaporated
  2. customresidue purified by flash column (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-4f2563316ef741d489239db8f278cb36
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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