Hydrochloric Acid → HCID 136377148, compound

HRID 1027212Notes

Reaction equation

HRID 1027212 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([C:15]2[O:16][C:17]([CH3:20])=[CH:18][N:19]=2)[CH:12]=[C:11]([O:21]C)[C:10]=1[C:23]1[N:28]=[N:27][C:26]([N:29]([CH3:40])[CH:30]2[CH2:35][C:34]([CH3:37])([CH3:36])[NH:33][C:32]([CH3:39])([CH3:38])[CH2:31]2)=[CH:25][CH:24]=1)C1C=CC=CC=1.[H][H].Cl.CO>[Pd].C(Cl)Cl.C(OCC)C.C(OCC)(=O)C.CO>[CH3:1][O:8][C:9]1[C:10]([C:23]2[N:28]=[N:27][C:26]([N:29]([CH3:40])[CH:30]3[CH2:35][C:34]([CH3:36])([CH3:37])[NH:33][C:32]([CH3:39])([CH3:38])[CH2:31]3)=[CH:25][CH:24]=2)=[C:11]([OH:21])[CH:12]=[C:13]([C:15]2[O:16][C:17]([CH3:20])=[CH:18][N:19]=2)[CH:14]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 86710610HCID 86710610, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 136377148HCID 136377148, compoundYield 73.8%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 21584119Ethylacetate methanolSolvent

Procedure

To a solution of 6-(2-(benzyloxy)-6-methoxy-4-(5-methyloxazol-2-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine (36 mg, 0.066 mmol) in 1:1 ethyl acetate/MeOH (1.3 mL) under an atmosphere of nitrogen was added palladium on carbon (10% Pd content, 7 mg, 6.6 umol). The atmosphere was replaced by hydrogen (balloon) and the mixture stirred rapidly at RT overnight. The solution was diluted with DCM and filtered through celite. The filtrate was concentrated to a yellow residue and acidified with HCl in MeOH (produced by slow addition of acetyl chloride (14 uL, 0.199 mmol) to 1 mL MeOH). The solution was concentrated under vacuum, the residue redissolved into MeOH, and loaded onto an SCX column preconditioned with MeOH. The column was washed with MeOH (20 mL) and eluted with 3.5 N ammonia in MeOH (20 mL). Evaporation of the eluent afforded the product as a light yellow residue. Sonication with diethyl ether resulted in formation of a light yellow solid. Solvent was removed under reduced pressure to provide 3-methoxy-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(5-methyloxazol-2-yl)phenol (22 mg). LCMS Rt=0.54 min (LCMS method Q); MS=352.3 (M+1). 1H NMR (400 MHz, METHANOL-d4) δ ppm 8.22 (d, J=10.11 Hz, 1H), 7.18-7.29 (m, 3H), 6.96 (d, J=1.01 Hz, 1H), 5.07-5.20 (m, 1H), 3.98 (s, 3H), 3.03 (s, 3H), 2.46 (d, J=1.52 Hz, 3H), 1.73 (dd, J=12.5, 3.4 Hz, 2H), 1.62 (t, J=12.5 Hz, 2H), 1.42 (s, 6H), 1.26 (s, 6H).

Workup

  1. filtrationfiltered through celite
  2. concentrationThe filtrate was concentrated to a yellow residue
  3. concentrationThe solution was concentrated under vacuum
  4. dissolutionthe residue redissolved into MeOH
  5. washThe column was washed with MeOH (20 mL)
  6. washeluted with 3.5 N ammonia in MeOH (20 mL)
  7. customEvaporation of the eluent
  8. customafforded the product as a light yellow residue
  9. customresulted in formation of a light yellow solid
  10. customSolvent was removed under reduced pressure

Sources & evidence

ORD record
ord-c8de85ecfb944541b0b4f8bd3bfc0ed1
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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