1-Hydroxybenzotriazole → HCID 67118599, compound

HRID 1189020Notes

Reaction equation

HRID 1189020 reaction equation
[CH3:1][CH:2]([O:4][C:5]1[CH:6]=[C:7]([O:23][C:24]2[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[CH:26][N:25]=2)[CH:8]=[C:9]2[C:13]=1[NH:12][C:11]([C:14]1[S:15][CH:16]([CH2:19][C:20]([OH:22])=O)[CH2:17][N:18]=1)=[CH:10]2)[CH3:3].Cl.[CH2:35]([N:37]=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.Cl.CN>O.CN(C)C=O.C(N(CC)CC)C>[CH3:35][NH:37][C:20](=[O:22])[CH2:19][CH:16]1[S:15][C:14]([C:11]2[NH:12][C:13]3[C:9]([CH:10]=2)=[CH:8][C:7]([O:23][C:24]2[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:31])=[O:32])=[CH:26][N:25]=2)=[CH:6][C:5]=3[O:4][CH:2]([CH3:3])[CH3:1])=[N:18][CH2:17]1

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6364545Methylamine hydrochlorideHCID 58236984HCID 58236984, compound

Product 1

HCID 67118599HCID 67118599, compoundYield 58.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

A mixture of {2-[7-(1-methylethoxy)-5-{[5-(methylsulfonyl)pyridin-2-yl]oxy}-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetic acid (200 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (120 mg), 1-hydroxybenzotriazole (80 mg), methylamine hydrochloride (60 mg), triethylamine (70 mg) and N,N-dimethylformamide (3 mL) was stirred at room temperature for 15 h. Water was added to the mixture and the resultant was extracted with ethyl acetate. The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution and brine, dried (MgSO4), filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (ethyl acetate:methanol=100:0 to 95:5, volume ratio) to give colorless crystals. The crystals were recrystallized from ethyl acetate-hexane to give the title compound (120 mg, 57%) as colorless prisms. MS 503 (MH+). mp 190-192° C.

Workup

  1. extractionthe resultant was extracted with ethyl acetate
  2. washThe organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution and brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel chromatography (ethyl acetate:methanol=100:0 to 95:5, volume ratio)
  7. customto give colorless crystals
  8. customThe crystals were recrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-be85a853dc6748edbef2f709a15b3a67
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

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