Acetic Anhydride → N-{2-Acetamido-2-[3-(trifluoromethyl)phenyl]propyl}-2-{3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-4,5-dihydro-1H-1,2,4-triazol-1-yl}acetamide

HRID 709159Notes

Reaction equation

HRID 709159 reaction equation
C(N(CC)C(C)C)(C)C.[C:10](OC(=O)C)(=[O:12])[CH3:11].[NH2:17][C:18]([C:45]1[CH:50]=[CH:49][CH:48]=[C:47]([C:51]([F:54])([F:53])[F:52])[CH:46]=1)([CH3:44])[CH2:19][NH:20][C:21](=[O:43])[CH2:22][N:23]1[C:27](=[O:28])[N:26]([CH2:29][C@H:30]([OH:35])[C:31]([F:34])([F:33])[F:32])[C:25]([C:36]2[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][CH:37]=2)=[N:24]1>ClCCl>[C:10]([NH:17][C:18]([C:45]1[CH:50]=[CH:49][CH:48]=[C:47]([C:51]([F:54])([F:53])[F:52])[CH:46]=1)([CH3:44])[CH2:19][NH:20][C:21](=[O:43])[CH2:22][N:23]1[C:27](=[O:28])[N:26]([CH2:29][C@H:30]([OH:35])[C:31]([F:34])([F:33])[F:32])[C:25]([C:36]2[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][CH:37]=2)=[N:24]1)(=[O:12])[CH3:11]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 81531DiisopropylethylamineHCID 87085301N-{2-Amino-2-[3-(trifluoromethyl)phenyl]propyl}-2-{3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-4,5-dihydro-1H-1,2,4-triazol-1-yl}acetamide

Product 1

HCID 56848557N-{2-Acetamido-2-[3-(trifluoromethyl)phenyl]propyl}-2-{3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-4,5-dihydro-1H-1,2,4-triazol-1-yl}acetamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

At RT, 12 μl (68 μmol) of N,N-diisopropylethylamine and then 6 μl (62 μmol) of acetic anhydride were added to a solution of 38 mg (62 μmol) of the compound of Example 53A in 0.96 ml of dichloromethane, and the mixture was stirred for 1 h. The volatile components were then removed on a rotary evaporator. Since LC/MS analysis of the crude product indicated additional formation of an O-acetylated byproduct, the residue was dissolved in 2 ml of methanol and 800 μl of 2 N aqueous sodium hydroxide solution were added. After 72 h, the mixture was acidified with 1 N hydrochloric acid and separated by preparative HPLC [Method 8]. In this step, the two product diastereomers were obtained in separated form. This gave 6 mg (16% of theory) of the title compound (Diastereomer 1) and 7 mg (19% of theory) of the second diastereomer (see Example 39).

Workup

  1. customThe volatile components were then removed on a rotary evaporator
  2. dissolutionthe residue was dissolved in 2 ml of methanol
  3. addition800 μl of 2 N aqueous sodium hydroxide solution were added
  4. waitAfter 72 h
  5. customseparated by preparative HPLC [Method 8]
  6. customIn this step, the two product diastereomers were obtained in separated form

Sources & evidence

ORD record
ord-b7eba6141e124116b265c3208a7d13f6
Source dataset
uspto-grants-2015_11
Patent number
US09180120B2

Reaction notes

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