1-Hydroxybenzotriazole → HCID 22496448, compound

HRID 1816184Notes

Reaction equation

HRID 1816184 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([CH:13]([C:24]3[CH:29]=[CH:28][C:27]([O:30][C:31]([F:34])([F:33])[F:32])=[CH:26][CH:25]=3)[CH2:14][C:15]3[CH:23]=[CH:22][C:18]([C:19](O)=[O:20])=[CH:17][CH:16]=3)[S:11][CH:12]=2)=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.Cl.C[O:59][C:60](=[O:64])[CH2:61][CH2:62][NH2:63]>CN(C=O)C.CO.C1COCC1.[OH-].[Na+].C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[C:10]([CH:13]([C:24]3[CH:29]=[CH:28][C:27]([O:30][C:31]([F:32])([F:34])[F:33])=[CH:26][CH:25]=3)[CH2:14][C:15]3[CH:16]=[CH:17][C:18]([C:19]([NH:63][CH2:62][CH2:61][C:60]([OH:64])=[O:59])=[O:20])=[CH:22][CH:23]=3)[S:11][CH:12]=2)=[CH:6][CH:7]=1

Participants

10

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2734767Methyl 3-aminopropanoate hydrochlorideHCID 22496388HCID 22496388, compound

Product 1

HCID 22496448HCID 22496448, compoundYield 70.7%

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Procedure

4-[2-[4-(4-Chlorophenyl)thiazol-2-yl]-2-(4-trifluoromethoxyphenyl)ethyl]benzoic acid (0.16 g, 0.31 mmol) was dissolve in DMF (5 mL) and 1-hydroxybenzotriazole (51.48 mg, 0.38 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (73 mg, 0.38 mmol) were added and the mixture was stirred at room temperature for 1.5 hours. DI PEA (0.123 g, 0.95 mmol) and 3-aminopropionic acid methyl ester hydrochloride (66 mg, 0.48 mmol) were added to the mixture. The mixture was heated at 40° C. for 2 hours and left with stirring for 16 hours at room temperature. Ethyl acetate (5 mL) was added and the mixture was washed with water (5 mL). The aqueous phase was extracted with ethyl acetate (5 mL). The combined organic phases were washed with brine (5 mL) and water (5 mL) and concentrated in vacuo to afford crude intermediary ester compound. The ester was dissolved in a mixture of methanol (4 mL) and THF (1 mL) and 4M sodium hydroxide (0.2 mL) was added. The mixture was stirred for 16 hours at room temperature and the solvents were removed by evaporation in vacuo. Water (6 mL) was added and the pH was adjusted (1-2) by the addition of 1M hydrochloric acid. The precipitate was filtered off, washed with water and dried to afford 126 mg (69%) of the title compound as a solid.

Workup

  1. temperatureThe mixture was heated at 40° C. for 2 hours
  2. waitleft
  3. stirringwith stirring for 16 hours at room temperature
  4. washthe mixture was washed with water (5 mL)
  5. extractionThe aqueous phase was extracted with ethyl acetate (5 mL)
  6. washThe combined organic phases were washed with brine (5 mL) and water (5 mL)
  7. concentrationconcentrated in vacuo
  8. customto afford crude intermediary ester compound
  9. additionwas added
  10. stirringThe mixture was stirred for 16 hours at room temperature
  11. customthe solvents were removed by evaporation in vacuo
  12. additionWater (6 mL) was added
  13. additionby the addition of 1M hydrochloric acid
  14. filtrationThe precipitate was filtered off
  15. washwashed with water
  16. customdried

Sources & evidence

ORD record
ord-fa779f8a642d4adfa161bdf07e7599c8
Source dataset
uspto-grants-2005_04
Patent number
US06881746B2

Reaction notes

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