Hydrochloric Acid → 6-(4-(1-aminocyclopropyl)phenyl)-1-methyl-7-phenyl-1H-pyrido[2,3-b][1,4]oxazin-2(3H)-one

HRID 1509327Notes

Reaction equation

HRID 1509327 reaction equation
C(OC(=O)[NH:7][C:8]1([C:11]2[CH:16]=[CH:15][C:14]([C:17]3[C:18]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[CH:19][C:20]4[N:25]([CH3:26])[C:24](=[O:27])[CH2:23][O:22][C:21]=4[N:28]=3)=[CH:13][CH:12]=2)[CH2:10][CH2:9]1)(C)(C)C.Cl.C(OCC)C>O1CCOCC1>[NH2:7][C:8]1([C:11]2[CH:12]=[CH:13][C:14]([C:17]3[C:18]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[CH:19][C:20]4[N:25]([CH3:26])[C:24](=[O:27])[CH2:23][O:22][C:21]=4[N:28]=3)=[CH:15][CH:16]=2)[CH2:9][CH2:10]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 131734408tert-butyl(1-(4-(1-methyl-2-oxo-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclopropyl)carbamate

Product 1

HCID 532626696-(4-(1-aminocyclopropyl)phenyl)-1-methyl-7-phenyl-1H-pyrido[2,3-b][1,4]oxazin-2(3H)-oneYield 57.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of tert-butyl(1-(4-(1-methyl-2-oxo-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclopropyl)carbamate (60 mg, 0.127 mmol) in 1,4-dioxane (1 mL) was added dropwise 4M HCl in 1,4-dioxane (0.5 mL, 2.00 mmol) and the resulting solution stirred at room temperature for 1 hour. The reaction mixture was diluted by the dropwise addition of diethyl ether (6 mL) and stirred for 15 minutes to give a white precipitate. The layers were allowed to settle and the supernatant solution removed. The solid was washed twice more with diethyl ether (6 mL), allowing to settle and removing the supernatant solvent each time. The remaining solvent was removed by concentration to dryness under reduced pressure, then freeze-drying over the weekend to give the desired product as an off-white solid (27 mg, 52% yield). 1H-NMR (500 MHz, MeOD) δ 7.53 (1H, s), 7.34 (2H, d), 7.31 (2H, d), 7.25-7.29 (3H, m), 7.18-7.23 (2H, m), 4.94 (2H, s), 3.41 (3H, s), 1.29-1.35 (2H, m), 1.24-1.29 (2H, m). LCMS (Method D): RT=0.75 min, M+H+=372.10.

Workup

  1. stirringstirred for 15 minutes
  2. customto give a white precipitate
  3. customthe supernatant solution removed
  4. washThe solid was washed twice more with diethyl ether (6 mL)
  5. customremoving the supernatant solvent each time
  6. customThe remaining solvent was removed by concentration to dryness under reduced pressure
  7. customfreeze-drying over the weekend

Sources & evidence

ORD record
ord-73d2ffdfe9de427cb451be2e3a83b2d7
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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