Trifluoroacetic acid → HCID 86690804, compound

HRID 1471764Notes

Reaction equation

HRID 1471764 reaction equation
C[O:2][CH:3](OC)[C:4]1[CH:9]=[CH:8][N:7]=[CH:6][C:5]=1[O:10][CH2:11][C:12]1[N:17]=[CH:16][C:15]([C:18]([NH:20][S:21]([CH3:24])(=[O:23])=[O:22])=[O:19])=[CH:14][CH:13]=1.[F:27][C:28]([F:33])([F:32])[C:29]([OH:31])=[O:30]>ClCCl>[F:27][C:28]([F:33])([F:32])[C:29]([OH:31])=[O:30].[CH:3]([C:4]1[CH:9]=[CH:8][N:7]=[CH:6][C:5]=1[O:10][CH2:11][C:12]1[CH:13]=[CH:14][C:15]([C:18]([NH:20][S:21]([CH3:24])(=[O:22])=[O:23])=[O:19])=[CH:16][N:17]=1)=[O:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86690806HCID 86690806, compound

Product 1

HCID 86690804HCID 86690804, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

Into a 50-mL round-bottom flask, which was purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 6-([[4-(dimethoxymethyl)pyridin-3-yl]oxy]methyl)-N-methanesulfonylpyridine-3-carboxamide (80 mg, 0.21 mmol, 1.00 equiv) in dichloromethane (5 mL), and trifluoroacetic acid (2 mL). The resulting solution was stirred for 3 h at 40° C. in an oil bath, and then it was concentrated under vacuum. The crude product (60 mg) was purified by Flash-Prep-HPLC with the following conditions (CombiFlash-1): Column, C18 silica gel; mobile phase, CH3CN/H2O=1/99 increasing to CH3CN/H2O=40/60 within 20 min; Detector, UV 254 nm. This resulted in 20 mg (17%) of 6-[[(4-formylpyridin-3-yl)oxy]methyl]-N-methanesulfonylpyridine-3-carboxamide; bis(trifluoroacetic acid) as a white solid. The compound exhibited a melting point of 102-104° C. LC-MS: (ES, m/z):336 [M+1]+/354 [M+1+18]+. H-NMR (300 MHz, DMSO, ppm): 10.53 (s, 1H), 9.07 (s, 1H), 8.78 (s, 1H), 8.43 (d, J=4.5 Hz, 1H), 8.36 (dd, J=8.1 Hz, 1H), 7.84 (d, J=8.4 Hz, 1H), 7.62 (d, J=4.5 Hz, 1H), 5.60 (s, 2H), 3.37 (s, 3H).

Workup

  1. customInto a 50-mL round-bottom flask, which was purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. concentrationit was concentrated under vacuum
  4. customThe crude product (60 mg) was purified by Flash-Prep-HPLC with the following conditions (CombiFlash-1)
  5. waitmobile phase, CH3CN/H2O=1/99 increasing to CH3CN/H2O=40/60 within 20 min
  6. customThis resulted in 20 mg (17%) of 6-[[(4-formylpyridin-3-yl)oxy]methyl]-N-methanesulfonylpyridine-3-carboxamide

Sources & evidence

ORD record
ord-02c8aae63d9f462989fe7607b957bf78
Source dataset
uspto-grants-2015_04
Patent number
US09012450B2

Reaction notes

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