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 589086Notes

Reaction equation

HRID 589086 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]([C:25]5[CH2:26][CH2:27][N:28]([C:31](OC(C)(C)C)=[O:32])[CH2:29][CH:30]=5)=[N:24][C:10]([C:11]=34)=[CH:9][CH:8]=2)=[C:5]([CH3:38])[O:4][N:3]=1.Cl.O1CCOC[CH2:41]1>CO>[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])[CH3:41]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86299168tert-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]-3,6-dihydropyridine-1(2H)-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 70%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

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]-3,6-dihydropyridine-1(2H)-carboxylate (3 mg, 0.006 mmol) was dissolved in methanol (0.5 mL) at room temperature, followed by addition of 4.0 M hydrogen chloride in dioxane (0.5 mL, 2 mmol) [Aldrich, cat. #345547]. The resulting mixture was stirred at room temperature for 10 min. The solvents were removed under a flow of nitrogen gas. 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 (1.8 mg, 70%). LCMS for C24H26O2N5 (M+H)+: calculated m/z=416.2. found 416.2.

Workup

  1. customThe solvents were removed under a flow of nitrogen gas
  2. customPurification by preparative LCMS (XBridge C18 column
  3. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

Sources & evidence

ORD record
ord-812fcc52249b4690aebc045ed43319b5
Source dataset
uspto-grants-2016_01
Patent number
US09227985B2

Reaction notes

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