Triethylamine → HCID 22065230, compound

HRID 1373348Notes

Reaction equation

HRID 1373348 reaction equation
[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=3)=[CH:14][CH:15]=2)[C:10]([C:28](=[O:32])[C:29](O)=[O:30])=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.Cl.[C:52]([O:56][C:57](=[O:60])[CH2:58][NH2:59])([CH3:55])([CH3:54])[CH3:53].C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)Cl>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:25])[F:26])=[CH:19][CH:18]=3)=[CH:14][CH:15]=2)[C:10]([C:28](=[O:32])[C:29]([NH:59][CH2:58][C:57]([O:56][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:60])=[O:30])=[CH:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 2725036Glycine tert-butyl ester hydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 6450819Tiplasinin

Product 1

HCID 22065230HCID 22065230, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To an ice-cooled solution of 2-{1-benzyl-5-[4-(trifluoromethoxy)phenyl]-1H-indol-3-yl}-2-oxoacetic acid (1.47 g, 3.35 mmol) in methylene chloride (25 mL) was added 1-hydroxybenzotriazole hydrate (0.771 g, 5.03 mmol). The reaction mixture was stirred for few minutes in an ice bath. Triethylamine (0.47 mL, 3.4 mmol), and glycine tert-butyl ester hydrochloride (0.573 g, 3.42 mmol) were added. After stirring for five more minutes in the ice bath, dicyclohexylcarbodiimide (0.88 g, 4.27 mmol) was added. The reaction mixture was then stirred at room temperature for 2 hours under nitrogen. The mixture was filtered. The insoluble matter was washed with ethyl acetate. The combined filtrate was evaporated to dryness. The residue was partitioned in ethyl acetate and 2N hydrochloric acid. The organic phase was washed with brine and evaporated to dryness. The residue was purified by flash chromatography (Biotage apparatus) using 2.5–12.5% ethyl acetate in hexane to yield the title compound as a yellow solid (1.47 g, 80%), mp 167–168° C. Mass spectrum (−ESI, [M−H]−) m/z 551.7; 1HNMR (500 MHz, DMSO-d6): δ9.05 (s, 1H), 9.0 (t, 1H, J=6.0 Hz), 8.5 (d, 1H, J=1.5 Hz), 7.75–7.8 (m, 2H), 7.7 (d, 1H, J=8.4 Hz), 7.6 (dd, 1H, J=8.6 Hz and 1.8 Hz), 7.45 (d, 1H, J=8.1 Hz), 7.3–7.35 (m, 5H), 5.65 ppm (s, 2H), 3.9 (d, 2H, J=6.1 Hz), and 1.45 ppm (s, 9H).

Workup

  1. additionwas added
  2. stirringThe reaction mixture was then stirred at room temperature for 2 hours under nitrogen
  3. filtrationThe mixture was filtered
  4. washThe insoluble matter was washed with ethyl acetate
  5. customThe combined filtrate was evaporated to dryness
  6. customThe residue was partitioned in ethyl acetate
  7. washThe organic phase was washed with brine
  8. customevaporated to dryness
  9. customThe residue was purified by flash chromatography (Biotage apparatus)

Sources & evidence

ORD record
ord-595498a169c84a8d967cf031473b1a6a
Source dataset
uspto-grants-2007_01
Patent number
US07160918B2

Reaction notes

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