Hydrochloric Acid → HCID 21949970, compound

HRID 2215754Notes

Reaction equation

HRID 2215754 reaction equation
CC([O-])(C)C.[K+].C1COCC1.[NH:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14]([CH2:21][C:22]([NH2:24])=[O:23])=[CH:13]1.C([O:27][C:28](=O)[C:29]([C:31]1[CH:32]=[CH:33][CH:34]=[C:35]2[C:39]=1[N:38]([CH3:40])[CH:37]=[CH:36]2)=O)C.Cl>CN(C=O)C.CCOC(C)=O>[NH:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14]([C:21]2[C:22](=[O:23])[NH:24][C:28](=[O:27])[C:29]=2[C:31]2[CH:32]=[CH:33][CH:34]=[C:35]3[C:39]=2[N:38]([CH3:40])[CH:37]=[CH:36]3)=[CH:13]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 397Indole-3-acetamideHCID 8028TetrahydrofuranHCID 23665647Potassium tert-butoxideHCID 69642171HCID 69642171, compound

Product 1

HCID 21949970HCID 21949970, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A 1.0 M solution of KOtBu in THF (6 mL, 6 mmol) was added to a solution of 2-(1H-indol-3-yl)-acetamide (296 mg, 1.70 mmol) and (1-methyl-1H-indol-7-yl)-oxo-acetic acid ethyl ester (381 mg, 1.65 mmol) in DMF (20 mL). The deep red-orange solution was stirred 7 h at 60° C., allowed to cool overnight and 1N HCl added. The orange mixture was poured into EtOAc, and the EtOAc layer was separated and washed with 1N HCl, water (3×), saturated aq NaHCO3 (2×) and brine, dried (MgSO4), filtered and concentrated onto SiO2. Flash chromatography (1:1 EtOAc:hexanes) afforded the title compound as a 1:1 solvate with EtOAc (514 mg, 72%) as a bright orange-red solid. Heating under vacuum at 70° C. afforded material which was used without further purification. 1H NMR (400 MHz, DMSO-d6) 11.85 (br s, 1H), 11.13 (s, 1H), 7.93 (d, J=3 Hz, 1H), 7.61 (dd, J=8, 1.5 Hz, 1H), 7.33 (d, J=8 Hz, 1H), 7.26 (d, J=3 Hz, 1H), 6.93–7.0 (m, 2H), 6.88 (d, J=7 Hz, 1H), 6.46–6.52 (d, J=7 Hz, 1H), 6.35 (d, J=7 Hz, 1H), 3.68 (s, 3H). MS (electrospray, m/z) 342.1 (M++1), 340.2 (M−−1). HRMS 342.1249 (M++1, calcd for C21H16N3O2 342.1242).

Workup

  1. temperatureto cool overnight
  2. customthe EtOAc layer was separated
  3. washwashed with 1N HCl, water (3×), saturated aq NaHCO3 (2×) and brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated onto SiO2

Sources & evidence

ORD record
ord-6d897be54e134b709e66c64168b25b98
Source dataset
uspto-grants-2006_09
Patent number
US07109229B2

Reaction notes

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