Hydrochloric Acid → HCID 25165895, compound

HRID 1873680Notes

Reaction equation

HRID 1873680 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](=CC=C3)[CH2:27][CH2:26][CH2:25][N:24]4[CH:23]=2)[CH2:9]1)=O)(C)(C)C.Cl.O1[CH2:40][CH2:39]OCC1.[CH3:41][CH2:42][N:43](C(C)C)C(C)C.[CH2:50](Cl)Cl>C(N=C=O)C>[CH2:42]([NH:43][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:25]4[C:26](=[CH:27][CH:28]=[CH:33]3)[CH2:40][CH2:39][CH2:50][N:24]4[CH:23]=2)[CH2:9]1)=[O:5])[CH3:41]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 6344DichloromethaneHCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 59404392HCID 59404392, compound

Product 1

HCID 25165895HCID 25165895, compoundYield 47%

Reagents, catalysts & solvents 1

HCID 8022Ethyl isocyanateCatalyst

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 (0.20 g, 0.45 mmol) in DCM (5 mL) was added 4M HCl in dioxane (1.7 mL, 6.8 mmol). After 2 hours the reaction mixture was concentrated and the residue taken up in DCM (5 mL). DIPEA (0.32 mL, 1.70 mmol) and ethyl isocyanate (42 μL, 0.53 μmol) were added and the reaction mixture stirred at room temperature overnight. Solids were filtered off and washed with DCM to give (3R,4R)-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)-pyrrolidine-1-carboxylic acid ethylamide as white crystals (88 mg, 47%). M.p.=278-279° C.; 1H NMR (400 MHz, DMSO-d6) δ: 10.80 (s, 1H), 7.57 (d, J=8.0 Hz, 1H), 7.39 (d, J=7.6 Hz, 1H), 7.29 (d, J=8.0 Hz, 1H), 7.20 (d, J=2.4 Hz, 1H), 7.17 (s, 1H), 7.02 (t, J=8.0 Hz, 1H), 6.93 (t, J=7.2 Hz, 1H), 6.85 (t, J=7.6 Hz, 1H), 6.77 (d, J=6.8 Hz, 1H), 6.14 (t, J=5.6 Hz, 1H), 4.03-3.94 (m, 6H), 3.41-3.32 (m, 2H), 3.11-3.04 (m, 2H), 2.84 (t, J=6.0 Hz, 2H), 2.04 (t, J=5.2 Hz, 2H), 1.03 (t, J=7.2 Hz, 3H). LCMS: m/e 413.16 [M+H].

Workup

  1. concentrationAfter 2 hours the reaction mixture was concentrated
  2. filtrationSolids were filtered off
  3. washwashed with DCM

Sources & evidence

ORD record
ord-6de3108d5ed448908ee52ae834c47c63
Source dataset
uspto-grants-2012_11
Patent number
US08304425B2

Reaction notes

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