Hydrochloric Acid → HCID 25165897, compound

HRID 1873683Notes

Reaction equation

HRID 1873683 reaction equation
C([O:5][C:6]([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]1(C(Cl)=O)[CH2:53][CH2:52][CH2:51]1>C(Cl)Cl>[CH:50]1([C:6]([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:5])[CH2:53][CH2:52][CH2:51]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 78705Cyclobutanecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 59404392HCID 59404392, compound

Product 1

HCID 25165897HCID 25165897, compoundYield 35,852.199%

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 cyclobutylcarbonyl chloride (64 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) and recrystallised from methanol to yield cyclobutyl-[(3R,4R)-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)-pyrrolidin-1-yl]-methanone as a white solid 82 mg, 43%). M.p.=253-255° C.; 1H NMR (400 MHz, DMSO-d6) δ: 10.80 (dd, J=8.0 and 2.0 Hz, 1H), 7.54 (dd, J=17.6 and 8.0 Hz, 1H), 7.36 (dd, J=18.0, 8.0 Hz, 1H), 7.27 (d, J=8.0 Hz, 1H), 7.20-7.16 (m, 2H), 7.01 (t, J=7.6 Hz, 1H), 6.93-6.88 (m, 1H), 6.86-6.81 (m, 1H), 6.76 (m, 1H), 4.10-3.87 (m, 6H), 3.52-3.29 (m, 3H), 2.82 (t, J=6.0 Hz, 2H), 2.24-2.00 (m, 6H), 1.87 (m, 1H), 1.75 (m, 1H). LCMS: m/e 424.16 [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)
  9. customrecrystallised from methanol

Sources & evidence

ORD record
ord-f12e5d0ac8784fedaf4d12cfacfb69ff
Source dataset
uspto-grants-2012_11
Patent number
US08304425B2

Reaction notes

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