Hydrochloric Acid → HCID 59404398, compound

HRID 1873681Notes

Reaction equation

HRID 1873681 reaction equation
C(OC([N:8]1[CH2:12][C@@H:11]([C:13]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[NH:15][CH:14]=2)[C@H:10]([C:22]2[C:32]3=[C:33]4[C:28](=[CH:29][CH:30]=[CH:31]3)[CH2:27][CH2:26][CH2:25][N:24]4[CH:23]=2)[CH2:9]1)=O)(C)(C)C.Cl.O1CCOCC1.CCN(C(C)C)C(C)C.[C:50]1([S:56](Cl)(=[O:58])=[O:57])[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1>C(Cl)Cl>[C:50]1([S:56]([N:8]2[CH2:12][C@@H:11]([C:13]3[C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[NH:15][CH:14]=3)[C@H:10]([C:22]3[C:32]4=[C:33]5[C:28](=[CH:29][CH:30]=[CH:31]4)[CH2:27][CH2:26][CH2:25][N:24]5[CH:23]=3)[CH2:9]2)(=[O:58])=[O:57])[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 7369Benzenesulfonyl chlorideHCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 59404392HCID 59404392, compound

Product 1

HCID 59404398HCID 59404398, compoundYield 51,909.398%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (3R,4R)-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (200 mg, 450 μmol) in DCM (5 mL) under a nitrogen atmosphere was added 4M HCl in dioxane (1.7 mL, 6.8 mmol). The mixture was stirred at room temperature for 2 h. The solvent was then removed under vacuum and the residue dissolved in DCM (5 mL). DIPEA (320 μL, 1.8 mmol) and benzenesulfonyl chloride (95 mg, 0.54 μmol) were added and the mixture stirred at room temperature for 16 h. The solvent was removed under vacuum. The residue was dissolved in DCM, washed with saturated sodium carbonate solution and water and evaporated. The residue was purified by column chromatography (SiO2, EtOAc/hexanes) to yield 1-[(3R,4R)-1-benzenesulfonyl-4-(1H-indol-3-yl)-pyrrolidin-3-yl]-5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline as a white solid (135 mg, 57%). M.p.=115-125° C.; 1H NMR (400 MHz, DMSO-d6) δ: 10.81 (s, 1H), 7.96 (d, J=8.0 Hz, 2H), 7.86 (t, J=7.6 Hz, 1H), 7.75 (t, J=8.0 Hz, 2H), 7.26 (d, J=8.0 Hz, 1H), 7.16 (d, J=7.6 Hz, 1H), 7.09 (d, J=6.4 Hz, 1H), 7.04 (s, 1H), 7.00 (t, J=7.6 Hz, 1H), 6.92 (dd, J=7.2, 2.0 Hz, 1H), 6.86 (t, J=7.6 Hz, 1H), 6.79-6.74 (m, 2H), 4.00-3.90 (m, 4H), 3.78-3.69 (m, 2H), 3.39-3.29 (m, 2H), 2.81 (t, J=6.0 Hz, 2H), 2.01 (m, 2H). LCMS: m/e 482.09 [M+H].

Workup

  1. customThe solvent was then removed under vacuum
  2. dissolutionthe residue dissolved in DCM (5 mL)
  3. stirringthe mixture stirred at room temperature for 16 h
  4. customThe solvent was removed under vacuum
  5. dissolutionThe residue was dissolved in DCM
  6. washwashed with saturated sodium carbonate solution and water
  7. customevaporated
  8. customThe residue was purified by column chromatography (SiO2, EtOAc/hexanes)

Sources & evidence

ORD record
ord-c6af6fe658234b4785ca331ab585da0f
Source dataset
uspto-grants-2012_11
Patent number
US08304425B2

Reaction notes

Loading…