Hydrochloric Acid → (4S)-2-(1-Acetylpiperidin-4-yl)-7-(3,5-dimethylisoxazol-4-yl)-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazine

HRID 589087Notes

Reaction equation

HRID 589087 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[C:16]3[O:15][CH2:14][C@H:13]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=4)[N:12]4[C:23]([CH:25]5[CH2:30][CH2:29][N:28]([C:31](OC(C)(C)C)=[O:32])[CH2:27][CH2:26]5)=[N:24][C:10]([C:11]=34)=[CH:9][CH:8]=2)=[C:5]([CH3:38])[O:4][N:3]=1.Cl.[CH2:40](N(CC)CC)C.C(Cl)(=O)C>CO.O1CCOCC1>[C:31]([N:28]1[CH2:29][CH2:30][CH:25]([C:23]2[N:12]3[C@@H:13]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=4)[CH2:14][O:15][C:16]4=[C:11]3[C:10](=[CH:9][CH:8]=[C:7]4[C:6]3[C:2]([CH3:1])=[N:3][O:4][C:5]=3[CH3:38])[N:24]=2)[CH2:26][CH2:27]1)(=[O:32])[CH3:40]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 86299169tert-Butyl 4-[(4S)-7-(3,5-dimethylisoxazol-4-yl)-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2-yl]piperidine-1-carboxylate

Product 1

HCID 86299170(4S)-2-(1-Acetylpiperidin-4-yl)-7-(3,5-dimethylisoxazol-4-yl)-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazineYield 81%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

To the solution of tert-butyl 4-[(4S)-7-(3,5-dimethylisoxazol-4-yl)-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2-yl]piperidine-1-carboxylate (8.8 mg, 0.017 mmol) in methanol (1 mL) was added 4.0 M hydrogen chloride in dioxane (1 ml) at room temperature. The resulting mixture was stirred at room temperature for 10 min. The solvents were then evaporated under a steam of nitrogen. Triethylamine (0.23 mL, 1.7 mmol) was added to the resulting residue, followed by acetyl chloride (0.029 mL, 0.41 mmol). The mixture was then stirred under a stream of nitrogen for 5 min at room temperature, followed by removal of solvents and residual reagents. Purification by preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) afforded the title compound (6.3 mg, 81%). LCMS for C26H28O3N5 (M+H)+: calculated m/z=458.2. found 458.2.

Workup

  1. customThe solvents were then evaporated under a steam of nitrogen
  2. stirringThe mixture was then stirred under a stream of nitrogen for 5 min at room temperature
  3. customfollowed by removal of solvents and residual reagents
  4. customPurification by preparative LCMS (XBridge C18 column
  5. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

Sources & evidence

ORD record
ord-04f92494525a45d2be5e754483512fd0
Source dataset
uspto-grants-2016_01
Patent number
US09227985B2

Reaction notes

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