Acetaldehyde → HCID 11295224, compound

HRID 916697Notes

Reaction equation

HRID 916697 reaction equation
[F:1][C:2]([F:33])([F:32])[CH2:3][S:4]([NH:7][C:8]([C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17]2[N:21]([CH3:22])[N:20]=[C:19]([CH2:23][NH:24][C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[CH:18]=2)[CH:12]=1)([CH3:10])[CH3:9])(=[O:6])=[O:5].[CH:34](=O)[CH3:35]>CC#N.CC(O)=O>[F:33][C:2]([F:1])([F:32])[CH2:3][S:4]([NH:7][C:8]([C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17]2[N:21]([CH3:22])[N:20]=[C:19]([CH2:23][N:24]([CH2:34][CH3:35])[C:25]3[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=3)[CH:18]=2)[CH:12]=1)([CH3:9])[CH3:10])(=[O:6])=[O:5]

Participants

5

Reactant 2

HCID 177AcetaldehydeHCID 11167630HCID 11167630, compound

Product 1

HCID 11295224HCID 11295224, compoundYield 12%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6342AcetonitrileSolvent

Procedure

NaB(CN)H3 (16 mg, 0.25 mmol) was added to a stirred solution of 2,2,2-trifluoro-N-[1-(3-{3-[(4-fluorophenylamino)methyl]-1-methyl-1H-pyrazol-5-yl}phenyl)-1-methylethyl]ethanesulfonamide (Example 3) (61 mg, 0.13 mmol) and acetaldehyde (11 mg, 0.25 mmol) in MeCN (5 mL), and AcOH (1 drop) and the mixture was stirred at RT for 16 hours. The mixture was concentrated under reduced pressure and then partitioned between NaHCO3 solution (20 mL) and EtOAc (70 mL). The organics were washed with brine (20 mL) and concentrated under reduced pressure whilst dry loading onto MgSO4. This residue was then purified by column chromatography on silica eluting with 100% Et2O and then by normal phase preparative HPLC to yield the desired product (7.6 mg, 12%). 1H NMR (CDCl3, 500 MHz) δ 7.55-7.48 (2H, m), 7.45 (1H, t, J=7.6 Hz), 7.32 (1H, d, J=7.6 Hz), 6.91 (2H, t, J=9 Hz), 6.78-6.71 (2H, m), 6.13 (1H, s), 4.91 (1H, s), 4.44 (2H, s), 3.85 (3H, s), 3.50-3.39 (4H, m), 1.80 (6H, s), 1.18 (3H, t, J=7.1 Hz). MS (ES+) C24H28F4N4O2S requires: 512, found: 513 (M+H+, 100%).

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. custompartitioned between NaHCO3 solution (20 mL) and EtOAc (70 mL)
  3. washThe organics were washed with brine (20 mL)
  4. concentrationconcentrated under reduced pressure
  5. customwhilst dry loading onto MgSO4
  6. customThis residue was then purified by column chromatography on silica eluting with 100% Et2O

Sources & evidence

ORD record
ord-dfc57a9502564017a8c00c4fbc80bab9
Source dataset
uspto-grants-2007_09
Patent number
US07271191B2

Reaction notes

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