Indole-3-acetamide → 3-(5,6-Dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione

HRID 541013

Reaction equation

HRID 541013 reaction equation
[O:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([CH2:15][C:16]([NH2:18])=[O:17])=[CH:7]1>C(OC)(C)(C)C>[C:8]1([C:15]2[C:16](=[O:17])[NH:18][C:5](=[O:1])[C:4]=2[C:3]2[C:9]3[C:14](=[CH:13][CH:12]=[CH:11][CH:10]=3)[NH:6][CH:2]=2)[C:9]2=[C:14]3[C:13](=[CH:12][CH:11]=[CH:10]2)[CH2:15][CH2:8][CH2:7][N:6]3[CH:7]=1

Participants

4

Reactant 2

HCID 397Indole-3-acetamide2×HCID 8028Tetrahydrofuran

Product 1

HCID 99692093-(5,6-Dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent2×

Procedure

In step 1 of scheme I, lilolidine (Compound 4), was treated with oxalylchloride to give the acyl chloride in methyl tert-butyl ether (MTBE) reaction solvent. The addition of methanol was sufficient to afford the intermediate ketoester, 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)oxoacetic acid methyl ester (Compound 5). In Step 2 of the reaction, Compound 5 and indole-3-acetamide (Compound 5a) were combined to produce 3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)pyrrole-2,5-dione (Compound 6). As described in detail in the following examples, it is not necessary to isolate intermediate Compound 5 to produce Compound 6. A solvent swap from MTBE into tetrahydrofuran (THF) was necessary prior to conducting Step 2, since both 5 and 5a have very poor solubility in MTBE. Following the addition of Compound 5a to consume Compound 5 in THF in the presence of base, HCl was added to complete the reaction to afford crude Compound 6. Crude Compound 6 was then purified from DCM and heptane to afford Compound 6 of sufficient purity to proceed to the next step. A detailed description of this process is shown in Example 1.

Workup

  1. customto consume Compound 5 in THF in the presence of base, HCl
  2. additionwas added
  3. customthe reaction
  4. customto afford crude Compound 6
  5. customCrude Compound 6 was then purified from DCM and heptane

Sources & evidence

ORD record
ord-7868fe3661b84adeabc278b63eaac887
Source dataset
uspto-grants-2014_10
Patent number
US08871933B2

Linked notes

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