Trifluoroacetic acid → HCID 66559224, compound

HRID 2405956Notes

Reaction equation

HRID 2405956 reaction equation
[CH3:1][C@@:2]([S:20]([CH3:23])(=[O:22])=[O:21])([CH2:6][CH2:7][N:8]1[C:12]([CH3:13])=[C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:10]=[N:9]1)[C:3](O)=[O:4].C[C@@](S(C)(=O)=O)(CCN1C(C2C=CC=CC=2)=C(C)N=N1)C(O)=O.CN1CCOCC1.O1CCCCC1[O:60][NH2:61].C(O)(C(F)(F)F)=O>C1COCC1>[OH:60][NH:61][C:3](=[O:4])[C@:2]([CH3:1])([S:20]([CH3:23])(=[O:22])=[O:21])[CH2:6][CH2:7][N:8]1[C:12]([CH3:13])=[C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:10]=[N:9]1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 70817556HCID 70817556, compoundHCID 70817818HCID 70817818, compound

Product 1

HCID 66559224HCID 66559224, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (2R)-2-methyl-4-(5-methyl-4-phenyl-1H-1,2,3-triazol-1-yl)-2-(methylsulfonyl)butanoic acid and (2R)-2-methyl-4-(4-methyl-5-phenyl-1H-1,2,3-triazol-1-yl)-2-(methylsulfonyl)butanoic acid (115 mg, 0.341 mmol, 1 eq) in THF (5 mL) was added N-methyl morpholine (65.5 mg, 0.341 mmol, 1 eq), and CDMT (59.9 mg, 0.341 mmol, 1 eq). The reaction mixture was allowed to stir at RT for 1 h then O-tetrahydro-2H-pyran-2-yl-hydroxylamine (39.9 mg 0.341 mmol, 1 eq) was added and the reaction mixture was allowed to stir at RT for 2 days. Upon completion of the coupling reaction (as observed by LC-MS monitoring), 1 mL of TFA was added and the mixture was allowed to stir at RT for 3 h. The reaction mixture was concentrated and purified by HPLC to give (2R)—N-hydroxy-2-methyl-4-(5-methyl-4-phenyl-1H-1,2,3-triazol-1-yl)-2-(methylsulfonyl)butanamide (14 mg) as a 10:1 mixture with the corresponding regioisomer (2R)—N-hydroxy-2-methyl-4-(4-methyl-5-phenyl-1H-1,2,3-triazol-1-yl)-2-(methylsulfonyl)butanamide. 1H NMR (400 MHz, METHANOL-d4) δ 7.61-7.67 (m, 2H), 7.43-7.50 (m, 2H), 7.38 (d, J=7.42 Hz, 1H), 4.51-4.63 (m, 1H), 4.36-4.48 (m, 1H), 3.06 (s, 3H), 2.85-2.93 (m, 1H), 2.51 (s, 3H), 2.43 (ddd, J=13.42, 10.10, 5.37 Hz, 1H), 1.72 (s, 3H). LC-MS M+H+353.1.

Workup

  1. stirringto stir at RT for 2 days
  2. additionwas added
  3. stirringto stir at RT for 3 h
  4. concentrationThe reaction mixture was concentrated
  5. custompurified by HPLC

Sources & evidence

ORD record
ord-e0af5097079f48f99c9ab1891661b0d1
Source dataset
uspto-grants-2014_08
Patent number
US08809333B2

Reaction notes

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