Benzenamine, 4-fluoro-N-(1-methylethyl)- → 4-(5-(((4-Fluorophenyl)(isopropyl)amino)methyl)thiophen-2-yl)benzaldehyde

HRID 717652Notes

Reaction equation

HRID 717652 reaction equation
O[CH2:2][C:3]1[S:7][C:6]([C:8]2[CH:15]=[CH:14][C:11]([CH:12]=[O:13])=[CH:10][CH:9]=2)=[CH:5][CH:4]=1.[F:16][C:17]1[CH:26]=[CH:25][C:20]([NH:21][CH:22]([CH3:24])[CH3:23])=[CH:19][CH:18]=1>C(Cl)Cl.CCN(CC)CC.C1(C)C=CC=CC=1>[F:16][C:17]1[CH:26]=[CH:25][C:20]([N:21]([CH2:2][C:3]2[S:7][C:6]([C:8]3[CH:15]=[CH:14][C:11]([CH:12]=[O:13])=[CH:10][CH:9]=3)=[CH:5][CH:4]=2)[CH:22]([CH3:24])[CH3:23])=[CH:19][CH:18]=1

Participants

6

Reactant 2

HCID 154403Benzenamine, 4-fluoro-N-(1-methylethyl)-HCID 87075020HCID 87075020, compound

Product 1

HCID 866606114-(5-(((4-Fluorophenyl)(isopropyl)amino)methyl)thiophen-2-yl)benzaldehydeYield 20%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

To a stirred solution of the product of Step A (0.436 g, 2 mmol) in anhydrous CH2Cl2 (10 ml) and Et3N (0.3 ml) mesyl chloride (0.4 ml) was added at 0° C. and stirring was continued for 1 h. The solvents were evaporated to dryness under reduced pressure and the residue was diluted to 50 ml with EtOAc and washed with H2O. The organic layer was separated and dried over MgSO4 and filtered. The filtrate was evaporated to give the crude product (0.63 g) as pale paste, which was taken up in anhydrous toluene and 4-fluoro-N-isopropylaniline (0.5 ml) was added to it. The mixture was stirred overnight at reflux and the solvent was evaporated. The residue was purified by FCC(SiO2, hexane/EtOAc) to give the title compound (0.14 g, 20%), as light creamy paste. 1H-NMR (CDCl3) 9.98 (s, 1H,); 7.82 (d, 2H, J=8.31 Hz); 7.66 (d, 2H, J=8.31 Hz); 7.28 (d, 1H, J=3.69 Hz); 6.93-6.86 (m, 3H); 6.81-6.76 (m, 2H); 4.79 (s, 2H); 4.08-3.99 (m, 1H); 1.22 (d, 6H, J=6.6 Hz).

Workup

  1. customThe solvents were evaporated to dryness under reduced pressure
  2. additionthe residue was diluted to 50 ml with EtOAc
  3. washwashed with H2O
  4. customThe organic layer was separated
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customThe filtrate was evaporated
  8. customto give the crude product (0.63 g) as pale paste, which
  9. stirringThe mixture was stirred overnight
  10. temperatureat reflux
  11. customthe solvent was evaporated
  12. customThe residue was purified by FCC(SiO2, hexane/EtOAc)

Sources & evidence

ORD record
ord-c37476af40484c118d72baef3dbd660e
Source dataset
uspto-grants-2015_11
Patent number
US09193716B2

Reaction notes

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