Trifluoroacetic acid → N-(pyrimidin-4-yl)-5-(2-(1,2,3,6-tetrahydropyridin-4-yl)-4-(trifluoromethyl)phenyl)naphthalene-2-sulfonamide 2,2,2-trifluoroacetate

HRID 1473313Notes

Reaction equation

HRID 1473313 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([NH:7][S:8]([C:11]2[CH:12]=[C:13]3[C:18](=[CH:19][CH:20]=2)[C:17]([C:21]2[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][C:22]=2[C:31]2[CH2:36][CH2:35][N:34](C(OC(C)(C)C)=O)[CH2:33][CH:32]=2)=[CH:16][CH:15]=[CH:14]3)(=[O:10])=[O:9])=[N:3][CH:2]=1.[F:44][C:45]([F:50])([F:49])[C:46]([OH:48])=[O:47]>C(Cl)Cl>[F:44][C:45]([F:50])([F:49])[C:46]([OH:48])=[O:47].[N:1]1[CH:6]=[CH:5][C:4]([NH:7][S:8]([C:11]2[CH:20]=[CH:19][C:18]3[C:13](=[CH:14][CH:15]=[CH:16][C:17]=3[C:21]3[CH:26]=[CH:25][C:24]([C:27]([F:28])([F:29])[F:30])=[CH:23][C:22]=3[C:31]3[CH2:36][CH2:35][NH:34][CH2:33][CH:32]=3)[CH:12]=2)(=[O:10])=[O:9])=[N:3][CH:2]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86687369tert-butyl 4-(2-(6-(N-(pyrimidin-4-yl)sulfamoyl)naphthalen-1-yl)-5-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate2×

Product 1

HCID 86687370N-(pyrimidin-4-yl)-5-(2-(1,2,3,6-tetrahydropyridin-4-yl)-4-(trifluoromethyl)phenyl)naphthalene-2-sulfonamide 2,2,2-trifluoroacetateYield 27.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A round bottom flask was charged with tert-butyl 4-(2-(6-(N-(pyrimidin-4-yl)sulfamoyl)naphthalen-1-yl)-5-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate (Intermediate Y) (0.031 g, 0.051 mmol) and DCM (0.508 mL) and trifluoroacetic acid (3.91 μl, 0.051 mmol) was added. The resulting solution was maintained at rt for 18 h and then concentrated. The residue was taken up in minimal MeOH/DMSO and purified by preparative HPLC (Phenomenex C18 150×30 mm, 5 μm: 25 to 85% CH3CN:H2O (1% TFA modifier) over 15 min). Fractions were combined and concentrated to afford N-(pyrimidin-4-yl)-5-(2-(1,2,3,6-tetrahydropyridin-4-yl)-4-(trifluoromethyl)phenyl)naphthalene-2-sulfonamide 2,2,2-trifluoroacetate (8.8 mg, 0.014 mmol) as a colorless film. 1H NMR (400 MHz, CD3OD) δ ppm 1.98-2.28 (m, 2H) 2.73-2.97 (m, 2H) 3.41-3.62 (m, 2H) 5.70 (dt, J=3.15, 1.60 Hz, 1H) 7.16 (dd, J=6.36, 1.08 Hz, 1H) 7.52 (d, J=8.02 Hz, 1H) 7.60 (dd, J=7.04, 1.17 Hz, 1H) 7.64 (d, J=9.00 Hz, 1H) 7.68-7.82 (m, 3H) 7.94 (dd, J=8.90, 1.96 Hz, 1H) 8.17 (d, J=8.31 Hz, 1H) 8.30 (d, J=6.06 Hz, 1H) 8.59 (s, 1H) 8.71 (d, J=1.86 Hz, 1H); m/z (ESI, +ve ion) 510.9 (M+H)+.

Workup

  1. additionwas added
  2. concentrationconcentrated
  3. custompurified by preparative HPLC (Phenomenex C18 150×30 mm, 5 μm: 25 to 85% CH3CN:H2O (1% TFA modifier) over 15 min)
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-0cefd9f57194418a91fac95b98c54a61
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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