1-Hydroxybenzotriazole → HCID 42637860, compound

HRID 1816172Notes

Reaction equation

HRID 1816172 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH2:25][C:26]2[CH:34]=[CH:33][C:29]([C:30]([OH:32])=O)=[CH:28][CH:27]=2)[C:9]2[S:10][CH:11]=[C:12]([C:14]3[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=3)[N:13]=2)=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.Cl.[CH3:58][O:59][C:60](=[O:64])[CH2:61][CH2:62][NH2:63]>CN(C=O)C.C(OCC)(=O)C>[CH3:58][O:59][C:60](=[O:64])[CH2:61][CH2:62][NH:63][C:30](=[O:32])[C:29]1[CH:33]=[CH:34][C:26]([CH2:25][N:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[C:9]2[S:10][CH:11]=[C:12]([C:14]3[CH:15]=[CH:16][C:17]([O:20][C:21]([F:22])([F:24])[F:23])=[CH:18][CH:19]=3)[N:13]=2)=[CH:27][CH:28]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2734767Methyl 3-aminopropanoate hydrochlorideHCID 224963614-{[(4-Chlorophenyl){4-[4-(trifluoromethoxy)phenyl]-1,3-thiazol-2-yl}amino]methyl}benzoic acid

Product 1

HCID 42637860HCID 42637860, compoundYield 109.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-({(4-Chlorophenyl)-[4-(4-trifluoromethoxyphenyl)thiazol-2-yl]amino}methyl)benzoic acid (47 g, 93 mmol) was dissolved in DMF (500 mL) and 1-hydoxybenzotriazole (18.9 g, 140 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (26.7 g, 140 mmol) were added and the mixture was stirred at room temperature for 1.5 hours. Di PEA (i 9.1 mL, 111 mmol) and 3-aminopropionic acid methyl ester hydrochloride (15.5 g, 111 mmol) were added to the mixture and the resulting mixture was stirred at room temperature for 16 hours. Ethyl acetate (500 mL) was added and the mixture was washed with water (500 mL). The aqueous phase was extracted with ethyl acetate (500 mL). The combined organic phases were washed with water (2×500 mL) and saturated aqueous ammonium chloride (2×300 mL), dried (Na2SO4) and concentrated in vacuo to afford 60 g (quant.) of crude 3-[4-({(4-chlorophenyl)-[4-(4-trifluoromethoxyphenyl)thiazol-2-yl]amino}methyl)benzoylamino]propionic acid methyl ester as a solid. Recrystallisation from ethanol afforded 31.2 g (55%) pure product.

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 16 hours
  2. washthe mixture was washed with water (500 mL)
  3. extractionThe aqueous phase was extracted with ethyl acetate (500 mL)
  4. washThe combined organic phases were washed with water (2×500 mL) and saturated aqueous ammonium chloride (2×300 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c034a312cc57420fba4f45c17626710f
Source dataset
uspto-grants-2005_04
Patent number
US06881746B2

Reaction notes

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