Hydrochloric Acid → HCID 73214446, compound

HRID 1398455Notes

Reaction equation

HRID 1398455 reaction equation
[CH3:1][C:2]1[N:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[N:9]([CH3:13])[C:8]1[CH:14]=[C:15]([O:24][CH2:25][C@@H:26]([NH:31]C(=O)OC(C)(C)C)[CH2:27][CH:28]([CH3:30])[CH3:29])[C:16]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=3)=[CH:17][C:7]2=1.Cl.O1CCOCC1.C([O-])(O)=O.[Na+]>CO.O>[NH2:31][C@@H:26]([CH2:27][CH:28]([CH3:30])[CH3:29])[CH2:25][O:24][C:15]1[C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)=[CH:17][C:7]2[C:6]3[C:11](=[C:2]([CH3:1])[N:3]=[CH:4][CH:5]=3)[C:10](=[O:12])[N:9]([CH3:13])[C:8]=2[CH:14]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 516892Sodium BicarbonateHCID 86710431HCID 86710431, compound

Product 1

HCID 73214446HCID 73214446, compoundYield 35.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of (S)-tert-butyl (1-((4,6-dimethyl-5-oxo-9-(pyridin-2-yl)-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (35 mg, 0.068 mmol) in Methanol (4 mL) was added HCl in 1,4-dioxane (0.169 mL, 0.677 mmol) at 0° C. Then the reaction mixture was stirred at RT for 2 h. The volatiles were concentrated under reduced pressure. The residue so obtained was basified with saturated aqueous NaHCO3, diluted with water and extracted with DCM (3×5 mL). The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The crude product was purified by reverse phase prep HPLC (Sunfire C18 column (19.0×150 mm) 10.0 micron; mobile phase A: 10 mM ammonium acetate in water; mobile phase B: acetonitrile; flow rate: 16.0 mL) to afford (S)-8-((2-amino-4-methylpentyl)oxy)-4,6-dimethyl-9-(pyridin-2-yl)benzo[c][2,7]naphthyridin-5(6H)-one (10 mg, 0.024 mmol, 35% yield) as an off-white solid. LC/MS (ESI) m/e 417.6 [(M+H)+, calcd for C25H29N4O2 417.2]; LC/MS retention time (method E): tR=0.84 min; HPLC retention time (method A): tR=7.61 min; HPLC retention time (method B): tR=8.29 min; 1H NMR (400 MHz, METHANOL-d4). 1H NMR (400 MHz, METHANOL-d4) δ ppm 8.70 (d, J=4.3 Hz, 1H), 8.64 (s, 1H), 8.58 (d, J=5.5 Hz, 1H), 8.21 (d, J=5.8 Hz, 1H), 8.04-7.94 (m, 1H), 7.93-7.86 (m, 1H), 7.46 (ddd, J=7.3, 5.0, 1.3 Hz, 1H), 7.18 (s, 1H), 4.32 (dd, J=9.5, 4.3 Hz, 1H), 4.13 (dd, J=9.4, 6.7 Hz, 1H), 3.84 (s, 3H), 3.36-3.34 (m, 1H), 3.11 (s, 3H), 1.86-1.70 (m, 1H), 1.53-1.32 (m, 2H), 0.97 (d, J=6.8 Hz, 3H), 0.93 (d, J=6.5 Hz, 3H).

Workup

  1. concentrationThe volatiles were concentrated under reduced pressure
  2. customThe residue so obtained
  3. extractionextracted with DCM (3×5 mL)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by reverse phase prep HPLC (Sunfire C18 column (19.0×150 mm) 10.0 micron; mobile phase A: 10 mM ammonium acetate in water; mobile phase B: acetonitrile; flow rate: 16.0 mL)

Sources & evidence

ORD record
ord-d0f6bdfabaeb4fb59f47bca9e180251e
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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