Acetic Acid → HCID 67248587, compound

HRID 1422902Notes

Reaction equation

HRID 1422902 reaction equation
[C:1]([O:5][C:6](=[O:14])[NH:7][CH:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[CH3:15][O:16][C:17]1[CH:18]=[C:19]2[C:28](=[CH:29][CH:30]=1)[N:27]=[CH:26][C:25]1[S:24][CH2:23][C:22](=O)[CH2:21][C:20]2=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(O)(=O)C.C([BH3-])#N.[Na+]>C1(C)C=CC=CC=1.CO>[C:1]([O:5][C:6](=[O:14])[NH:7][CH:8]1[CH2:13][CH2:12][N:11]([CH:22]2[CH2:21][C:20]3[C:19]4[C:28](=[CH:29][CH:30]=[C:17]([O:16][CH3:15])[CH:18]=4)[N:27]=[CH:26][C:25]=3[S:24][CH2:23]2)[CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 6101p-Toluenesulfonic acidHCID 7238334-(N-Boc-amino)piperidineHCID 5003444Sodium cyanoborohydrideHCID 67248929HCID 67248929, compound

Product 1

HCID 67248587HCID 67248587, compoundYield 28.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1140TolueneSolvent

Procedure

A solution of piperidin-4-yl-carbamic acid tert-butyl ester (2.45 g, 12.22 mmol, 2.0 eq), 6-methoxy-4H-1-thia-9-aza-phenanthren-3-one (1.50 g, 6.11 mmol, 1.0 eq) and p-toluenesulfonic acid (526 mg, 3.06 mmol, 0.5 eq) in toluene (50 mL) is heated at 120° C. for 2 hours. The resulting solution is cooled down to room temperature, solvent is removed and the crude is dissolved in dichloromethane (100 mL) and methanol (100 mL) before the addition of acetic acid (0.5 mL, 8.66 mmol, 1.4 eq) and sodium cyanoborohydride (1.24 g, 19.73 mmol, 3.2 eq). After 1 h30 stirring at room temperature, the reaction mixture is extracted with dichloromethane (3×50 mL) and a saturated sodium hydrogen carbonate aqueous solution (50 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a residue that is purified by column chromatography (silica gel, eluent: petroleum ether:ethyl acetate:ammonia-7N solution in methanol, 1:1:0.05, v/v/v) to afford [1-(6-methoxy-3,4-dihydro-2H-1-thia-9-aza-phenanthrene-3-yl)-piperidin-4-yl]-carbamic acid tert-butyl ester as a light yellow solid (746 mg, 28% yield).

Workup

  1. customsolvent is removed
  2. dissolutionthe crude is dissolved in dichloromethane (100 mL)
  3. extractionAfter 1 h30 stirring at room temperature, the reaction mixture is extracted with dichloromethane (3×50 mL)
  4. dry with materialThe combined organic layers are dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a residue that
  8. customis purified by column chromatography (silica gel, eluent: petroleum ether:ethyl acetate:ammonia-7N solution in methanol, 1:1:0.05, v/v/v)

Sources & evidence

ORD record
ord-1254d9dbf42b4df48b7187590abbf594
Source dataset
uspto-grants-2015_01
Patent number
US08927541B2

Reaction notes

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