Acetic Acid → HCID 71523527, compound

HRID 527448Notes

Reaction equation

HRID 527448 reaction equation
[Cl:1][C:2]1[CH:26]=[CH:25][C:5]([C:6]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([O:17][CH3:18])=[CH:14][CH:15]=3)[C:10]([CH3:19])=[C:9]2[CH2:20][CH2:21][C:22](O)=[O:23])=[O:7])=[CH:4][CH:3]=1.[CH3:27][S:28]([NH2:31])(=[O:30])=[O:29].[N+](=C1CCCCC2C1CCCC=2)=[N-].CC(O)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:26]=[CH:25][C:5]([C:6]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([O:17][CH3:18])=[CH:14][CH:15]=3)[C:10]([CH3:19])=[C:9]2[CH2:20][CH2:21][C:22]([NH:31][S:28]([CH3:27])(=[O:30])=[O:29])=[O:23])=[O:7])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 72879MethanesulfonamideHCID 22747271HCID 22747271, compoundHCID 57563344HCID 57563344, compound

Product 1

HCID 71523527HCID 71523527, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
2.5 °C

Procedure

To a cooled mixture (0-5° C.) of 3-(1-(4-chlorobenzoyl)-5-methoxy-3-methyl-1H-indol-2-yl)propanoic acid (40 mg, 0.11 mmol) in CH2Cl2 (1 mL), 1′1′-carbonyldiimidazole (CDI) (17.4 mg, 0.11 mmol) was added. After the mixture was stirred for 2 h at 0-5° C., methansulfonamide (10 mg, 0.11 mmol) and diazobicyclo-[5.4.0]undec-7-ene (DBU) (16.1 μL, 0.11 mmol) were added. The mixture was left stirring overnight. Glacial AcOH (13.2 μL) was added, the reaction mixture was diluted with CH2Cl2 (1 mL), and the organic layer was washed with 10% NaH2PO4 (pH 4) (1×1 mL) and water (3 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to give a crude residue that was purified by flash chromatography (SiO2, ethyl acetate/hexane, 0.5% AcOH gradient) to afford the title compound as a bright yellow solid (32 mg, 66%). C21H21ClN2O5S, Mr=448.92; 1H NMR (400 MHz, DMSO-d6) d: 2.21 (s, 3H), 2.55 (t, J=7.2 Hz, 2H), 3.11 (t, J=7.2 Hz, 2H), 3.16 (s, 3H), 3.75 (s, 3H), 6.43 (d, J=9.2 Hz, 1H), 6.64 (dd, J=9.0 Hz, 1H), 7.02 (d, J=2.4 Hz, 1H), 7.64-7.69 (m, 4H); LCMS (ESI) tR: 2.74 min (>95%, UV254, ELSD), m/z: 249.1 [M+1]+.

Workup

  1. waitThe mixture was left
  2. stirringstirring overnight
  3. washthe organic layer was washed with 10% NaH2PO4 (pH 4) (1×1 mL) and water (3 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give a crude residue that
  8. customwas purified by flash chromatography (SiO2, ethyl acetate/hexane, 0.5% AcOH gradient)

Sources & evidence

ORD record
ord-3560f5db3cc445d89570358698f2c5ec
Source dataset
uspto-grants-2016_05
Patent number
US09346803B2

Reaction notes

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