Trifluoroacetic acid → 2-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(5-(4-methylphenylsulfonamido)-1,2,4-oxadiazol-3-yl)benzyl)benzamido)acetic acid

HRID 923615Notes

Reaction equation

HRID 923615 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([OH:12])=O)=[C:5]([C:13]([F:16])([F:15])[F:14])[CH:4]=1.C(Cl)(=O)C(Cl)=O.[NH2:23][C:24]1[CH:63]=[CH:62][C:27]([C:28]([N:30]([CH2:54][C:55]([O:57]C(C)(C)C)=[O:56])[CH2:31][C:32]2[CH:37]=[CH:36][C:35]([C:38]3[N:42]=[C:41]([NH:43][S:44]([C:47]4[CH:52]=[CH:51][C:50]([CH3:53])=[CH:49][CH:48]=4)(=[O:46])=[O:45])[O:40][N:39]=3)=[CH:34][CH:33]=2)=[O:29])=[CH:26][CH:25]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl.CN(C=O)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([NH:23][C:24]2[CH:63]=[CH:62][C:27]([C:28]([N:30]([CH2:54][C:55]([OH:57])=[O:56])[CH2:31][C:32]3[CH:33]=[CH:34][C:35]([C:38]4[N:42]=[C:41]([NH:43][S:44]([C:47]5[CH:52]=[CH:51][C:50]([CH3:53])=[CH:49][CH:48]=5)(=[O:46])=[O:45])[O:40][N:39]=4)=[CH:36][CH:37]=3)=[O:29])=[CH:26][CH:25]=2)=[O:12])=[C:5]([C:13]([F:16])([F:15])[F:14])[CH:4]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 65578Oxalyl chlorideHCID 467375752-(4-Methoxy-2-(trifluoromethyl)phenyl)acetic acidHCID 89285147tert-butyl 2-(4-amino-N-(4-(5-(4-methylphenylsulfonamido)-1,2,4-oxadiazol-3-yl)benzyl)benzamido)acetate

Product 1

HCID 711122942-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(5-(4-methylphenylsulfonamido)-1,2,4-oxadiazol-3-yl)benzyl)benzamido)acetic acidYield 18%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

Prepared using General Procedures 7 and 8: To a stirring suspension of 2-(4-methoxy-2-(trifluoromethyl)phenyl)acetic acid (26.4 mg, 0.113 mmol) in DCM (1 mL) and DMF (10 μL) was added oxalyl chloride (9.85 μL, 0.113 mmol) at room temperature. After 1 h the reaction mixture was added to a solution of tert-butyl 2-(4-amino-N-(4-(5-(4-methylphenylsulfonamido)-1,2,4-oxadiazol-3-yl)benzyl)benzamido)acetate INT-69 (13 mg, 0.023 mmol) in DCM (0.5 mL) and TEA (6.27 μL, 0.045 mmol). After stirring at room temperature for 2 h TFA (0.5 mL) was added. The reaction mixture was concentrated in vacuo and purified by preparative HPLC to afford 3.2 mg (18%) of 2-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(5-(4-methylphenylsulfonamido)-1,2,4-oxadiazol-3-yl)benzyl)benzamido)acetic acid 480 as an off-white solid. LCMS-ESI (m/z) calculated for C35H30F3N5O8S: 737; found 738 [M+H]+, tR=5.74 min (Method 9).

Workup

  1. customPrepared
  2. additionwas added
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-5931e408eacd4a328d20765da3a3e6d5
Source dataset
uspto-grants-2016_03
Patent number
US09278910B2

Reaction notes

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