Hydrochloric Acid → HCID 25165896, compound

HRID 1873682Notes

Reaction equation

HRID 1873682 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.[CH:50]([S:53](Cl)(=[O:55])=[O:54])([CH3:52])[CH3:51]>C(Cl)Cl>[NH:15]1[C:16]2[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:13]([C@@H:11]2[CH2:12][N:8]([S:53]([CH:50]([CH3:52])[CH3:51])(=[O:55])=[O:54])[CH2:9][C@H:10]2[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)=[CH:14]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 824082-Propanesulfonyl chlorideHCID 59404392HCID 59404392, compound

Product 1

HCID 25165896HCID 25165896, compoundYield 41,787.398%

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 isopropylsulfonyl chloride (77 mg, 0.54 μmol) were added and the mixture stirred at room temperature for 16 h. The solvent was removed under vacuum and the residue 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)-4-(1H-indol-3-yl)-1-(propane-2-sulfonyl)-pyrrolidin-3-yl]-5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline as a white solid (101 mg, 50%). M.p.=100-115° C.; 1H NMR (400 MHz, DMSO-d6) δ: 10.85 (s, 1H), 7.56 (d, J=8.0 Hz, 1H), 7.39 (d, J=8.0 Hz, 1H), 7.29 (d, J=8.0 Hz, 1H), 7.26 (d, J=2.4 Hz, 1H), 7.23 (s, 1H), 7.03 (t, J=7.2 Hz, 1H), 6.94 (t, J=7.2 Hz, 1H), 6.86 (t, J=7.6 Hz, 1H), 6.78 (d, J=7.2 Hz, 1H), 4.07-3.95 (m, 6H), 3.55-3.46 (m, 3H), 2.84 (t, J=6.0 Hz, 2H), 2.05 (t, J=5.6 Hz, 2H), 1.32 (m, 6H). LCMS: m/e 448.13 [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 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-5cb50da30c674bc49bc745ed11d12ef3
Source dataset
uspto-grants-2012_11
Patent number
US08304425B2

Reaction notes

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