Hydrochloric Acid → 2-[2'-(3-Methoxypropyl)-3-methylbiphenyl-4-yl]-3-pyridin-3-ylpropan-1-amine bis hydrochloride salt

HRID 2194923Notes

Reaction equation

HRID 2194923 reaction equation
C(OC(=O)[NH:7][CH2:8][CH:9]([C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[CH2:29][CH2:30][CH2:31][O:32][CH3:33])=[CH:19][C:18]=1[CH3:34])[CH2:10][C:11]1[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=1)(C)(C)C.[ClH:36]>C(Cl)Cl.[Zn+2].[Br-].[Br-]>[ClH:36].[ClH:36].[CH3:33][O:32][CH2:31][CH2:30][CH2:29][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[C:20]1[CH:21]=[CH:22][C:17]([CH:9]([CH2:10][C:11]2[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=2)[CH2:8][NH2:7])=[C:18]([CH3:34])[CH:19]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 131730115Tert-butyl{2-[2'-(3-methoxypropyl)-3-methylbiphenyl-4-yl]-3-pyridin-3-ylpropyl}carbamate

Product 1

HCID 674482492-[2'-(3-Methoxypropyl)-3-methylbiphenyl-4-yl]-3-pyridin-3-ylpropan-1-amine bis hydrochloride salt

Reagents, catalysts & solvents 2

HCID 10421208Zinc bromideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl{2-[2′-(3-methoxypropyl)-3-methylbiphenyl-4-yl]-3-pyridin-3-ylpropyl}carbamate from step 3 (1 eq.) in CH2Cl2 (0.1M) was added ZnBr2 (10 eq.). The mixture was sonicated for 30 min, filtered on a plug of silica gel. The latter was washed with CH2Cl2/MeOH (NH3 2M) 10% and the combined fractions were concentrated. The residue was purified by reverse phase HPLC (C18 column; gradient 40 to 90% of CH3CN/H2O/TFA 0.1%). Fractions containing the desired material were combined, concentrated, neutralized with NaOH (1N) and extracted with CH2Cl2. The combined extract was dried over Na2SO4, filtered and concentrated. The residue was dissolved in CH2Cl2, acidified with HCl (4N in dioxane; 4 eq.) and the resulting suspension was triturated with addition of Et2O to afford after filtration the title compounds as a light yellow solid. 1H NMR (500 MHz, DMSO-d6): δ 8.71 (d, 1H), 8.67 (s, 1H), 8.27 (br s, 3H), 7.98 (d, 1H), 7.56 (brt, 1H), 7.47 (d, 1H), 7.31 (s, 1H), 7.30 (s, 1H), 7.28-7.22 (m, 1H), 7.18 (d, 1H), 7.12 (d, 1H), 7.02 (s, 1H), 3.74-3.64 (m, 1H), 3.45 (brdd, 1H), 3.21-3.17 (m, 4H), 3.13 (s, 3H), 3.04 (dd, 1H), 2.61-2.50 (m, 2H), 2.08 (s, 3H), 1.65-1.55 (m, 2H).

Workup

  1. customThe mixture was sonicated for 30 min
  2. filtrationfiltered on a plug of silica gel
  3. washThe latter was washed with CH2Cl2/MeOH (NH3 2M) 10%
  4. concentrationthe combined fractions were concentrated
  5. customThe residue was purified by reverse phase HPLC (C18 column; gradient 40 to 90% of CH3CN/H2O/TFA 0.1%)
  6. additionFractions containing the desired material
  7. concentrationconcentrated
  8. extractionextracted with CH2Cl2
  9. extractionThe combined extract
  10. dry with materialwas dried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. dissolutionThe residue was dissolved in CH2Cl2
  14. customthe resulting suspension was triturated with addition of Et2O
  15. customto afford
  16. filtrationafter filtration the title compounds as a light yellow solid

Sources & evidence

ORD record
ord-19502ab9795b4f298b3ecea1f0751ab8
Source dataset
uspto-grants-2012_12
Patent number
US08334308B2

Reaction notes

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