p-Toluenesulfonic acid → HCID 71626804, compound

HRID 1775237Notes

Reaction equation

HRID 1775237 reaction equation
[CH3:1][C:2]1([CH3:19])[CH2:14][C:13]2=[N:15][NH:16][C:17](=[O:18])[C:10]3[C:11]4[C:12]2=[C:4]([NH:5][C:6]=4[CH:7]=[CH:8][CH:9]=3)[CH2:3]1.Br[CH2:21][CH2:22][O:23]C1CCCCO1.C([O-])([O-])=O.[K+].[K+].CC1C=CC(S(O)(=O)=O)=CC=1>CN(C=O)C.O.CO>[OH:23][CH2:22][CH2:21][N:5]1[C:4]2[CH2:3][C:2]([CH3:19])([CH3:1])[CH2:14][C:13]3=[N:15][NH:16][C:17](=[O:18])[C:10]4[C:11]([C:12]=23)=[C:6]1[CH:7]=[CH:8][CH:9]=4

Participants

8

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 11430Potassium CarbonateHCID 866212-(2-Bromoethoxy)tetrahydro-2H-pyranHCID 136242904HCID 136242904, compound

Product 1

HCID 71626804HCID 71626804, compoundYield 69%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent3×HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 2,2-dimethyl-2,3,5,10-tetrahydro-[1,2]diazepino[3,4,5,6-def]carbazol-6(1H)-one (100 mg, 0.39 mmol) in dry DMF (8 mL) was added 2-(2-bromoethoxy)tetrahydro-2H-pyran (194 mg, 1.17 mmol). K2CO3 (215 mg, 1.6 mmol) was added and the mixture was heated at 70° C. for 11.5 hours. Then water (100 mL) was added to the mixture, which was then extracted with EA (50 mL×3). The organic layers were combined, washed with brine, dried over Na2SO4, and concentrated to provide crude yellow oil. Then MeOH (15 mL) was added to the residue, followed by the addition of p-TSA.H2O (100 mg, 0.52 mmol), and the mixture was stirred at room temperature for 1 hour. Water (100 mL) was added to the mixture, extracted with EA (50 mL×3). The organic layers were combined, washed with saturated aqueous NaHCO3 and brine, dried over Na2SO4, and concentrated The residue was purified by chromatography column on silica gel (elution with hexane/ethyl acetate) to give 80 mg (69% yield) of 10-(2-hydroxyethyl)-2,2-dimethyl-2,3,5,10-tetrahydro-[1,2]diazepino[3,4,5,6-def]carbazol-6(1H)-one as yellow solid. 1H NMR (DMSO-d6) δ 9.89 (s, 1H), 7.58 (d, 1H, J=8.4 Hz), 7.47 (d, 1H, J=7.2 Hz), 7.15 (dd, 1H, J=7.2, 8.4 Hz), 4.88 (t, 1H, J=5.4 Hz), 4.21 (t, 2H, J=5.4 Hz), 3.65-3.68 (m, 1H), 2.76 (s, 2H), 2.25 (s, 2H), and 1.07 (s, 6H). MS (ESI) m/e [M+1]+ 298.1.

Workup

  1. extractionwas then extracted with EA (50 mL×3)
  2. washwashed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customto provide crude yellow oil
  6. extractionextracted with EA (50 mL×3)
  7. washwashed with saturated aqueous NaHCO3 and brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated The residue
  10. customwas purified by chromatography column on silica gel (elution with hexane/ethyl acetate)

Sources & evidence

ORD record
ord-0ede1fb18c694f80a71d9e92f4efecaf
Source dataset
uspto-grants-2016_02
Patent number
US09260440B2

Reaction notes

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