1,2-Dichloroethane → Trifluoroacetic acid

HRID 2207399Notes

Reaction equation

HRID 2207399 reaction equation
ClCCl.C(Cl)CCl.[CH3:8][S:9]([NH2:12])(=[O:11])=[O:10].[CH3:13][C:14]1[CH:15]=[C:16]([C:31]2[CH:32]=[CH:33][C:34]([C:37](O)=[O:38])=[N:35][CH:36]=2)[CH:17]=[C:18]([NH:20][C:21]2[N:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[CH:23][N:22]=2)[CH:19]=1.CN([CH:43]=[O:44])C>CN(C1C=CN=CC=1)C.[Cl-].[NH4+]>[CH3:8][S:9]([NH:12][C:37]([C:34]1[CH:33]=[CH:32][C:31]([C:16]2[CH:17]=[C:18]([NH:20][C:21]3[N:26]=[C:25]([C:27]([F:30])([F:28])[F:29])[CH:24]=[CH:23][N:22]=3)[CH:19]=[C:14]([CH3:13])[CH:15]=2)=[CH:36][N:35]=1)=[O:38])(=[O:11])=[O:10].[C:43]([OH:44])([C:27]([F:30])([F:29])[F:28])=[O:10]

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 6228DimethylformamideHCID 6344DichloromethaneHCID 72879MethanesulfonamideHCID 118092560HCID 118092560, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 118104159HCID 118104159, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 25517Ammonium ChlorideSolvent

Procedure

Dichloromethane (670 μL), EDC (38 mg, 0.20 mmol), methylsulfonamide (25 mg, 0.27 mmol) and DMAP (1.6 mg, 0.013 mmol) were added to 5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridine-2-carboxylic acid (50 mg, 0.13) and the reaction was allowed to stir for 16 hours at room temperature. DMF (500 μL) was added to the reaction and stirred overnight at room temperature. The reaction was then diluted with aqueous saturated ammonium chloride and extracted with dichloromethane. The organic layer was washed with water, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by reverse phase HPLC (10-100% acetonitrile/water with 0.1% TFA) to afford N-(methylsulfonyl)-5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridine-2-carboxamide as a TFA salt. MS ESI calc'd for C19H17F3N5O3S [M+H]+ 452. found 452. 1H NMR (500 MHz, DMSO-d6) δ 10.45-10.28 (m, 1H), 9.05-8.91 (m, 1H), 8.92-8.78 (m, 1H), 8.39-8.25 (m, 1H), 8.25-8.12 (m, 1H), 8.12-8.02 (m, 1H), 7.71-7.57 (m, 1H), 7.44-7.21 (m, 1H), 3.39 (s, 3H), 2.40 (s, 3H).

Workup

  1. stirringstirred overnight at room temperature
  2. extractionextracted with dichloromethane
  3. washThe organic layer was washed with water
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by reverse phase HPLC (10-100% acetonitrile/water with 0.1% TFA)

Sources & evidence

ORD record
ord-9962b0faf11e47e0ace6c870d3f17763
Source dataset
uspto-grants-2016_06
Patent number
US09376418B2

Reaction notes

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