Methanol → tert-Butyl (3-((7-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-yl)oxy)propyl)carbamate

HRID 1027200Notes

Reaction equation

HRID 1027200 reaction equation
CCOC(C)=O.CO.C([O:16][C:17]1[CH:26]=[C:25]2[C:20]([CH:21]=[CH:22][C:23]([O:27][CH2:28][CH2:29][CH2:30][NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[CH:24]2)=[CH:19][C:18]=1[C:39]1[N:40]=[N:41][C:42]([N:45]([CH3:56])[CH:46]2[CH2:51][C:50]([CH3:53])([CH3:52])[NH:49][C:48]([CH3:55])([CH3:54])[CH2:47]2)=[CH:43][CH:44]=1)C1C=CC=CC=1>C(Cl)Cl.CCOCC.[Pd]>[OH:16][C:17]1[CH:26]=[C:25]2[C:20]([CH:21]=[CH:22][C:23]([O:27][CH2:28][CH2:29][CH2:30][NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[CH:24]2)=[CH:19][C:18]=1[C:39]1[N:40]=[N:41][C:42]([N:45]([CH3:56])[CH:46]2[CH2:51][C:50]([CH3:53])([CH3:52])[NH:49][C:48]([CH3:55])([CH3:54])[CH2:47]2)=[CH:43][CH:44]=1

Participants

7

Reactant 3

HCID 887MethanolHCID 8857Ethyl AcetateHCID 86710597Tert-butyl (3-((7-(benzyloxy)-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-yl)oxy)propyl)carbamate

Product 1

HCID 136377147tert-Butyl (3-((7-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-yl)oxy)propyl)carbamateYield 91.1%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

Pd/C (10% wt 80 mg, 0.075 mmol) was added to a EtOAc (5 mL)/MeOH (5 mL) solution of tert-butyl (3-((7-(benzyloxy)-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-yl)oxy)propyl)carbamate (492 mg, 0.752 mmol) at RT. The reaction mixture was evacuated and filled with H2 (2×) then stirred at RT under H2 (1 atm) for 16 h. The reaction mixture was filtered through celite washing with MeOH, wash then concentrated in vacuo to dryness affording a tan solid. The solid was dissolved in DCM then adsorbed onto a silica bound amine column (Si—NH2 column 10 g, Varian brand, Bond Elut NH2). The column was then washed with MeOH (150 mL) then the solvent was concentrated in vacuo affording a yellow oil. The oil was dissolved in Et2O then concentrated in vacuo affording the title compound as a beige solid (386 mg, 91% yield). MS (M+1)=564.3; 1H NMR (400 MHz, DMSO-d6) δ ppm 13.29 (br. s, 1H), 8.34 (s, 1H), 8.28 (d, J=10.10 Hz, 1H), 7.76 (d, J=9.09 Hz, 1H), 7.34 (d, J=10.11 Hz, 1H), 7.15 (s, 1H), 7.08 (d, J=2.53 Hz, 1H), 6.94 (dd, J=9.09, 2.53 Hz, 1H), 4.89-5.06 (m, 1H), 4.56 (s, 1H), 4.09 (t, J=6.32 Hz, 2H), 3.09-3.16 (m, 2H), 2.98 (s, 3H), 1.80-1.95 (m, 2H), 1.50-1.61 (m, 2H), 1.44 (t, J=12.38 Hz, 2H), 1.38 (s, 9H), 1.27 (s, 6H), 1.10 (s, 6H).

Workup

  1. customThe reaction mixture was evacuated
  2. additionfilled with H2 (2×)
  3. filtrationThe reaction mixture was filtered
  4. washthrough celite washing with MeOH
  5. washwash
  6. concentrationthen concentrated in vacuo to dryness
  7. customaffording a tan solid
  8. washThe column was then washed with MeOH (150 mL)
  9. concentrationthe solvent was concentrated in vacuo
  10. customaffording a yellow oil
  11. concentrationthen concentrated in vacuo

Sources & evidence

ORD record
ord-c7b5adb3a856488f964d2726d402aca6
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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