Hydrochloric Acid → (S)-4-methyl-1((2-methyl-5H-chromeno[3,4-c]pyridin-8-yl)oxy)pentan-2-amine

HRID 870979Notes

Reaction equation

HRID 870979 reaction equation
[CH3:1][CH:2]([CH3:30])[CH2:3][C@H:4]([NH:22][C:23](=[O:29])[O:24]C(C)(C)C)[CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10]2[C:20]3[C:15](=[CH:16][N:17]=[C:18]([CH3:21])[CH:19]=3)[CH2:14][O:13][C:11]=2[CH:12]=1.Cl.O1CCOC[CH2:33]1>CO.C(#N)C>[C:23]([O-:24])(=[O:29])[CH3:33].[NH4+:17].[CH3:1][CH:2]([CH3:30])[CH2:3][C@H:4]([NH2:22])[CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10]2[C:20]3[C:15](=[CH:16][N:17]=[C:18]([CH3:21])[CH:19]=3)[CH2:14][O:13][C:11]=2[CH:12]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86724455(S)-tert-butyl (4-methyl-1-((2-methyl-5H-chromeno[3,4-c]pyridin-8-yl)oxy)pentan-2-yl)carbamate

Product 2

HCID 517165Ammonium AcetateYield 0.1%HCID 71727017(S)-4-methyl-1((2-methyl-5H-chromeno[3,4-c]pyridin-8-yl)oxy)pentan-2-amineYield 79.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of (S)-tert-butyl (4-methyl-1-((2-methyl-5H-chromeno[3,4-c]pyridin-8-yl)oxy)pentan-2-yl)carbamate (0.05 g, 0.121 mmol) in MeOH (2 mL) was added 4N HCl in 1,4-dioxane (0.5 mL, 16.46 mmol). The reaction mixture was stirred for 4 h at RT. The reaction mixture was then concentrated and the residue was dissolved in ethyl acetate (10 mL). The organic layer was washed with saturated NaHCO3 (2×10 mL) and water (20 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to afford a residue which was purified by prep. HPLC (0.1% ammonium acetate in acetonitrile) to afford (S)-4-methyl-1((2-methyl-5H-chromeno[3,4-c]pyridin-8-yl)oxy)pentan-2-amine (0.15 g, 0.048 mmol, 32% yield) as a gummy-solid. 1H NMR (400 MHz, CD3OD) δ 8.21 (s, 1H); 7.80 (d, J=8.80 Hz, 1H), 7.55 (s, 1H); 6.74 (d, J=10.80 Hz, 1H), 6.60 (d, J=2.40 Hz, 1H), 5.12 (s, 2H), 4.01-3.96 (m, 1H), 3.84-3.79 (m, 1H), 3.24-3.22 (m, 1H), 2.53 (s, 3H), 1.82-1.79 (m, 1H), 1.42-1.39 (m, 2H), 0.99-0.95 (m, 6H); LCMS (ESI) m/e 312.5 [(M)+, calcd for C19H24N2O2 312.2]; LC/MS retention time (Method E): tR=1.63 min; HPLC retention time (method A): tR=7.96 min; HPLC retention time (method B): tR=9.01 min.

Workup

  1. concentrationThe reaction mixture was then concentrated
  2. dissolutionthe residue was dissolved in ethyl acetate (10 mL)
  3. washThe organic layer was washed with saturated NaHCO3 (2×10 mL) and water (20 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto afford a residue which
  8. customwas purified by prep

Sources & evidence

ORD record
ord-8fe2e728a597449eaefe6d43319e9a12
Source dataset
uspto-grants-2015_03
Patent number
US08969564B2

Reaction notes

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