Trifluoroacetic acid → 7-(3-Amino-propoxy)-3-{6-[methyl-(2,2,6,6-tetramethyl-piperidin-4-yl)-amino]-pyridazin-3-yl}-naphthalen-2-ol

HRID 1027201Notes

Reaction equation

HRID 1027201 reaction equation
C(O)(C(F)(F)F)=O.[OH:8][C:9]1[CH:18]=[C:17]2[C:12]([CH:13]=[CH:14][C:15]([O:19][CH2:20][CH2:21][CH2:22][NH:23]C(=O)OC(C)(C)C)=[CH:16]2)=[CH:11][C:10]=1[C:31]1[N:32]=[N:33][C:34]([N:37]([CH3:48])[CH:38]2[CH2:43][C:42]([CH3:45])([CH3:44])[NH:41][C:40]([CH3:47])([CH3:46])[CH2:39]2)=[CH:35][CH:36]=1>C(Cl)Cl.CO>[NH2:23][CH2:22][CH2:21][CH2:20][O:19][C:15]1[CH:16]=[C:17]2[C:12]([CH:11]=[C:10]([C:31]3[N:32]=[N:33][C:34]([N:37]([CH3:48])[CH:38]4[CH2:43][C:42]([CH3:44])([CH3:45])[NH:41][C:40]([CH3:47])([CH3:46])[CH2:39]4)=[CH:35][CH:36]=3)[C:9]([OH:8])=[CH:18]2)=[CH:13][CH:14]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 136377147tert-Butyl (3-((7-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-yl)oxy)propyl)carbamate

Product 1

HCID 1366337287-(3-Amino-propoxy)-3-{6-[methyl-(2,2,6,6-tetramethyl-piperidin-4-yl)-amino]-pyridazin-3-yl}-naphthalen-2-olYield 75%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

TFA (1.5 ml, 19.47 mmol) was added to a solution of Example 20-4 (289.4 mg, 0.513 mmol) in DCM (6 ml) at RT. The reaction mixture was stirred at RT for 30 min, diluted with MeOH then adsorbed onto a MeOH conditioned SCX column (10 g). The column was washed several times with MeOH then eluted with 3 N NH3 in MeOH. Evaporation of the solvent afforded the title compound as a beige solid (178 mg, 75% yield). LCMS Rt=0.44 min (LCMS method Q); MS (M+1)=464.2. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.35 (s, 1H), 8.28 (d, J=9.60 Hz, 1H), 7.77 (d, J=9.09 Hz, 1H), 7.36 (d, J=9.60 Hz, 1H), 7.16-7.18 (m, 1H), 7.11 (d, J=2.53 Hz, 1H), 6.96 (dd, J=8.84, 2.27 Hz, 1H), 4.91-5.04 (m, 1H), 4.56 (s, 1H), 4.17 (t, J=6.32 Hz, 2H), 2.98 (s, 3H), 2.88 (d, J=7.07 Hz, 2H), 1.90-2.05 (m, 2H), 1.46-1.62 (m, 4H), 1.30 (s, 6H), 1.14 (s, 6H).

Workup

  1. washThe column was washed several times with MeOH
  2. washthen eluted with 3 N NH3 in MeOH
  3. customEvaporation of the solvent

Sources & evidence

ORD record
ord-4c118b5df96a40c2a4ce657677e46375
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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