Hydrochloric Acid → 2-{3-(4-Chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-4,5-dihydro-1H-1,2,4-triazol-1-yl}-N-{2-formamido-2-[3-(trifluoromethyl)phenyl]propyl}acetamide

HRID 709160Notes

Reaction equation

HRID 709160 reaction equation
C(N(CC)C(C)C)(C)C.[CH:10](OC1C=CC([N+]([O-])=O)=CC=1)=[O:11].[NH2:22][C:23]([C:50]1[CH:55]=[CH:54][CH:53]=[C:52]([C:56]([F:59])([F:58])[F:57])[CH:51]=1)([CH3:49])[CH2:24][NH:25][C:26](=[O:48])[CH2:27][N:28]1[C:32](=[O:33])[N:31]([CH2:34][C@H:35]([OH:40])[C:36]([F:39])([F:38])[F:37])[C:30]([C:41]2[CH:46]=[CH:45][C:44]([Cl:47])=[CH:43][CH:42]=2)=[N:29]1.[OH-].[Li+].Cl>C1COCC1.O>[Cl:47][C:44]1[CH:45]=[CH:46][C:41]([C:30]2[N:31]([CH2:34][C@H:35]([OH:40])[C:36]([F:39])([F:38])[F:37])[C:32](=[O:33])[N:28]([CH2:27][C:26]([NH:25][CH2:24][C:23]([NH:22][CH:10]=[O:11])([C:50]3[CH:55]=[CH:54][CH:53]=[C:52]([C:56]([F:59])([F:58])[F:57])[CH:51]=3)[CH3:49])=[O:48])[N:29]=2)=[CH:42][CH:43]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 746284-Nitrophenyl formate2×HCID 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 870853032-{3-(4-Chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-4,5-dihydro-1H-1,2,4-triazol-1-yl}-N-{2-formamido-2-[3-(trifluoromethyl)phenyl]propyl}acetamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

At RT, 12 μl (68 μmol) of N,N-diisopropylethylamine and then 11 mg (65 μmol) of 4-nitrophenyl formate were added to a solution of 38 mg (62 μmol) of the compound of Example 53A in 1 ml of THF, and the mixture was stirred at RT. After 1 h, another 10 mg (62 μmol) of 4-nitrophenyl formate were added and stirring of the reaction mixture was continued overnight. Since LC/MS analysis indicated additional formation of an O-formylated byproduct, 248 μl of a 1 N solution of lithium hydroxide in water were added to the reaction mixture. After 1 h, the mixture was acidified with 1 N hydrochloric acid and separated by preparative HPLC [Method 8]. This gave 30 mg (81% of theory) of the title compound as a diastereomer mixture.

Workup

  1. stirringstirring of the reaction mixture
  2. waitwas continued overnight
  3. additionwere added to the reaction mixture
  4. waitAfter 1 h
  5. customseparated by preparative HPLC [Method 8]

Sources & evidence

ORD record
ord-e510a64fe8b84129b33641a36737339f
Source dataset
uspto-grants-2015_11
Patent number
US09180120B2

Reaction notes

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