p-Toluenesulfonic acid → HCID 71626803, compound

HRID 1775236Notes

Reaction equation

HRID 1775236 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.[H-].[Na+].Br[CH2:23][CH2:24][O:25]C1CCCCO1.CC1C=CC(S(O)(=O)=O)=[CH:37][CH:38]=1.CN(C=[O:47])C>CO.O>[OH:25][CH2:24][CH2:23][N:16]1[C:17](=[O:18])[C:10]2[C:11]3[C:12]4[C:13]([CH2:14][C:2]([CH3:19])([CH3:1])[CH2:3][C:4]=4[N:5]([CH2:37][CH2:38][OH:47])[C:6]=3[CH:7]=[CH:8][CH:9]=2)=[N:15]1

Participants

8

Reactant 5

HCID 6101p-Toluenesulfonic acidHCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 866212-(2-Bromoethoxy)tetrahydro-2H-pyranHCID 136242904HCID 136242904, compound

Product 1

HCID 71626803HCID 71626803, compoundYield 30%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent3×

Conditions

Temperature
0 °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 NaH (47 mg, 1.95 mmol) under ice bath. The reaction was stirred at 0° C. for 40 minutes. 2-(2-Bromoethoxy)tetrahydro-2H-pyran (194 mg, 1.17 mmol) was added to the mixture at 0° C. and the reaction was stirred at room temperature for 6 hours. Then water (100 mL) was added to the mixture, extracted with DCM (50 mL×3) and EA (50 mL×3). The organic layers were combined, washed with brine and dried over Na2SO4. The organic phase was concentrated to provide crude product. Then the crude product was dissolved in MeOH (15 mL), p-TSA.H2O (100 mg, 0.52 mmol) was added to the solution and the mixture was stirred at room temperature for 16 hours. Water (150 mL) was added to the mixture, extracted with EA (50 mL×3). The combined organic layers were washed with saturated aqueous NaHCO3 and brine, dried over Na2SO4, and concentrated The residue was purified by Pre-TLC (DCM/MeOH=10/1) to provide 40 mg (30%) of 5,10-bis(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 7.57 (m, 2H), 7.15 (dd, 1H, J=7.2, 8.4 Hz), 4.88 (t, 1H, J=5.4 Hz), 4.61 (t, 1H, J=6.0 Hz), 4.21 (t, 2H, J=5.4 Hz), 3.94 (t, 2H, J=6.6 Hz), 3.94 (t, 2H, J=6.6 Hz), 3.63-3.68 (m, 2H), 2.77 (s, 2H), 2.28 (s, 2H), and 1.08 (s, 6H). MS (ESI) m/e [M+1]+ 342.2.

Workup

  1. stirringthe reaction was stirred at room temperature for 6 hours
  2. extractionextracted with DCM (50 mL×3) and EA (50 mL×3)
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationThe organic phase was concentrated
  6. customto provide crude product
  7. stirringthe mixture was stirred at room temperature for 16 hours
  8. extractionextracted with EA (50 mL×3)
  9. washThe combined organic layers were washed with saturated aqueous NaHCO3 and brine
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated The residue
  12. customwas purified by Pre-TLC (DCM/MeOH=10/1)

Sources & evidence

ORD record
ord-e0c2b1363c3448c59e84973db69cc104
Source dataset
uspto-grants-2016_02
Patent number
US09260440B2

Reaction notes

Loading…