Trifluoromethanesulfonic acid → n-[2-(5-Chloro-3-pyridyl)-3-(4-chloro-3-iodophenyl)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide

HRID 488633

Reaction equation

HRID 488633 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH:9]([C:29]2[CH:30]=[N:31][CH:32]=[C:33]([Cl:35])[CH:34]=2)[CH:10]([NH:12][C:13](=[O:28])[C:14]([O:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][N:19]=2)([CH3:16])[CH3:15])[CH3:11])=[CH:4][CH:3]=1.[B-](F)(F)(F)F.C1C=CN=CC=1.C1C=CN=CC=1.[IH2+:53].OS(C(F)(F)F)(=O)=O.S(=O)(O)[O-].[Na+]>C(Cl)Cl>[Cl:35][C:33]1[CH:34]=[C:29]([CH:9]([CH2:8][C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([I:53])[CH:4]=2)[CH:10]([NH:12][C:13](=[O:28])[C:14]([O:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:25])[F:26])=[CH:20][N:19]=2)([CH3:15])[CH3:16])[CH3:11])[CH:30]=[N:31][CH:32]=1

Participants

6

Reactant 4

HCID 62406Trifluoromethanesulfonic acidHCID 10883201Bis(pyridine)iodonium tetrafluoroborateHCID 11983631n-[3-(4-Chlorophenyl)-2-(5-chloro-3-pyridyl)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamideHCID 23665763Sodium Bisulfite

Product 1

HCID 22270507n-[2-(5-Chloro-3-pyridyl)-3-(4-chloro-3-iodophenyl)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The procedure of Barluenga (J Org Chem 1990, 55, 3104) was used. Thus, to a solution of N-[3-(4-chlorophenyl)-2-(5-chloro-3-pyridyl)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide (Example 398, 22 mg, 0.041 mmol) and bis(pyridine)iodonium tetrafluoroborate (30 mg, 0.082 mmol) in 0.3 mL anhydrous CH2Cl2 was added triflic acid (18 μL, 0.20 mmol). After stirring at room temperature for 50 min, the reaction mixture was poured into a mixture of ice (20 g) and sodium bisulfite (1 g) and was extracted with EtOAc. The organic extracts were dried over anhydrous sodium sulfate, filtered and concentrated to dryness to give the crude product, which was purified by preparative HPLC eluting on a reverse-phase HPLC column with 75 to 100% water in acetonitrile (containing 0.1% trifluoroacetic acid) to give the title compound. 1H NMR (500 MHz, CD3OD): δ 8.43 (d, 1H), 8.32 (s, 1H), 8.10 (s, 1H), 8.04 (d, 1H), 7.99 (dd, 1H), 7.82 (m, 1H), 7.36 d, 1H), 7.22 (d, 1H), 7.08 (d, 1H), 6.78 (dd, 1H), 4.29 (m, 1H), 3.03 (dd, 1H), 2.94 (m, 1H), 2.64 (dd, 1H), 1.78 (s, 3H), 1.75 (s, 3H), 0.88 (d, 3H). LC-MS: m/e 652 (M+H)+ (4.1 min).

Workup

  1. extractionwas extracted with EtOAc
  2. dry with materialThe organic extracts were dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated to dryness
  5. customto give the crude product, which
  6. customwas purified by preparative HPLC
  7. washeluting on a reverse-phase HPLC column with 75 to 100% water in acetonitrile (containing 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-2951785611b64db596505943ba2118b4
Source dataset
uspto-grants-2005_12
Patent number
US06972295B2

Linked notes

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