Hydrochloric Acid → HCID 59404397, compound

HRID 1873684Notes

Reaction equation

HRID 1873684 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.[CH3:50][C:51]([CH3:57])([CH3:56])[CH2:52][C:53](Cl)=[O:54]>C(Cl)Cl>[C:22]1([C@H:10]2[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)[CH2:12][N:8]([C:53](=[O:54])[CH2:52][C:51]([CH3:57])([CH3:56])[CH3:50])[CH2:9]2)[C:32]2=[C:33]3[C:28](=[CH:29][CH:30]=[CH:31]2)[CH2:27][CH2:26][CH2:25][N:24]3[CH:23]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 815143,3-Dimethylbutanoyl chlorideHCID 81531DiisopropylethylamineHCID 59404392HCID 59404392, compound

Product 1

HCID 59404397HCID 59404397, compoundYield 44,654.199%

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 3,3-dimethylbutanoyl chloride (72 mg, 0.54 μmol) were added and the mixture stirred at roomt 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). The resulting solid was recrystallised from methanol to yield 1-[(3R,4R)-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)-pyrrolidin-1-yl]-3,3-dimethyl-butan-1-one as a white solid (106 mg, 53%). M.p.=202-204° C.; 1H NMR (400 MHz, DMSO-d6) δ: 10.82 (dd, J=7.2 and 1.6 Hz, 1H), 7.56 (dd, J=14.0 and 8.0 Hz, 1H), 7.38 (dd, J=13.6 and 8.0 Hz, 1H), 7.30-7.18 (m, 3H), 7.02 (t, J=8.0 Hz, 1H), 6.93 (m, 1H), 6.86 (m, 1H), 6.77 (m, 1H), 4.21-3.89 (m, 6H), 3.65-3.36 (m, 2H), 2.83 (t, J=5.6 Hz, 2H), 2.21 (s, 2H), 2.04 (m, 2H), 1.04 (s, 9H). LCMS: m/e 440.20 [M+H].

Workup

  1. customThe solvent was then removed under vacuum
  2. dissolutionthe residue dissolved in DCM (5 mL)
  3. stirringthe mixture stirred at roomt 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. customThe resulting solid was recrystallised from methanol

Sources & evidence

ORD record
ord-19fa39792ea14e8282b425d68b5e4c3d
Source dataset
uspto-grants-2012_11
Patent number
US08304425B2

Reaction notes

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