1,2-Dichloroethane → 5-(1-(4-chlorobenzyl)-1H-indole-2-carbonyl)octahydro-1H-pyrrolo[3,4-c]pyridin-1-one

HRID 83677Notes

Reaction equation

HRID 83677 reaction equation
[Cl:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH:9]=[C:8]2[C:16](O)=[O:17])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[C:44]1(=[O:53])[CH:52]2[CH:47]([CH2:48][NH:49][CH2:50][CH2:51]2)[CH2:46][NH:45]1>CN(C=O)C>[Cl:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH:9]=[C:8]2[C:16]([N:49]2[CH2:50][CH2:51][CH:52]3[C:44](=[O:53])[NH:45][CH2:46][CH:47]3[CH2:48]2)=[O:17])=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 20745767HCID 20745767, compoundHCID 223108991-(4-Chlorobenzyl)-1H-indole-2-carboxylic acid

Product 1

HCID 683797135-(1-(4-chlorobenzyl)-1H-indole-2-carbonyl)octahydro-1H-pyrrolo[3,4-c]pyridin-1-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The following was added sequentially to DMF (10 mL): 1-(4-chlorobenzyl)-1H-indole-2-carboxylic acid (250 mg, 0.875 mmol), DIPEA (0.46 mL, 2.64 mmol), EDC (202 mg, 1.050 mmol), and HOBT (162 mg, 1.050 mmol). This solution was allowed to stir at rt for 1 h, at which time crude octahydro-1H-pyrrolo[3,4-c]pyridin-1-one (˜123 mg, 0.875 mmol) was added. Stirring continued for 12 h at rt, at which time the solution was partitioned between water and 1:1 solution of ethyl acetate:diethyl ether. The organic extract was then washed with water (1×) and saturated aq. sodium carbonate (1×), dried with magnesium sulfate, and concentrated in vacuo. Purification was accomplished via silica gel flash chromatography (100 g silica, 100% EtOAc.) Resulting residue was crystallized from the in vacuo removal of DCM to give the title compound as a slightly pink solid. (Yield: 200 mg, 0.49 mmol, 56%) 1H NMR (400 MHz, CDCl3) 7.72, 7.40-7.24, 7.20, 7.17-7.11, 6.94, 6.31, 5.51, 4.57, 4.30-4.08, 3.59-3.46, 3.39, 3.17-3.02, 2.63, 2.51, 2.02-1.77

Workup

  1. additionwas added
  2. customthe solution was partitioned between water and 1:1 solution of ethyl acetate
  3. extractionThe organic extract
  4. washwas then washed with water (1×) and saturated aq. sodium carbonate (1×)
  5. dry with materialdried with magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customPurification
  8. customResulting residue
  9. customwas crystallized from the
  10. customin vacuo removal of DCM

Sources & evidence

ORD record
ord-cf51ca6194f141388fea402abfc3f233
Source dataset
uspto-grants-2014_09
Patent number
US08846684B2

Reaction notes

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