Triethylamine → HCID 86657109, compound

HRID 467970Notes

Reaction equation

HRID 467970 reaction equation
[F:1][CH:2]([F:12])[C:3]1[C:7]([C:8](Cl)=[O:9])=[CH:6][N:5]([CH3:11])[N:4]=1.[CH3:13][O:14][N:15]=[CH:16][C:17]1[CH:22]=[C:21]([Cl:23])[C:20]([O:24][CH2:25][C@@H:26]2[CH2:30][CH2:29][CH2:28][NH:27]2)=[C:19]([Cl:31])[CH:18]=1.C(N(CC)CC)C>ClCCl>[CH3:13][O:14][N:15]=[CH:16][C:17]1[CH:22]=[C:21]([Cl:23])[C:20]([O:24][CH2:25][C@@H:26]2[CH2:30][CH2:29][CH2:28][N:27]2[C:8]([C:7]2[C:3]([CH:2]([F:12])[F:1])=[N:4][N:5]([CH3:11])[CH:6]=2)=[O:9])=[C:19]([Cl:31])[CH:18]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 153401103-(Difluoromethyl)-1-methyl-1 H-pyrazole-4-carbonyl chlorideHCID 86657110HCID 86657110, compound

Product 1

HCID 86657109HCID 86657109, compoundYield 57.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

At a temperature of 0° C., a solution of 3-difluoromethyl-1-methyl-1H-pyrazole-4-carbonyl chloride (0.103 g; 0.53 mmol) in dichloromethane (4 ml) was added dropwise to a stirred solution of 3,5-dichloro-4-[(S)-1-pyrrolidin-2-ylmethoxy)-benzaldehyde O-methyl-oxime (0.16 g; 0.53 mmol), which was prepared in analogy as described for example P12, and triethylamine (146 μl; 1.05 mmol) in dichloromethane (7 ml). The ice bath was removed and reaction mixture was allowed stirring for 4 hours. The reaction mixture was washed with 2M HCl (10 ml), 1M NaOH (10 ml) and saturated NaCl (30 ml) and then dried over Na2SO4. After removal of the solvent, the residue (0.20 g in the form of an oil) was purified by flash chromatography over silica gel (eluent:cyclohexane/ethyl acetate 1:1). 0.14 g (57% of theory) of 3,5-dichloro-4-[(S)-1-(3-difluoromethyl-1-methyl-1H-pyrazole-4-carbonyl)-pyrrolidin-2-ylmethoxy]-benzaldehyde O-methyl-oxime was obtained in form of an oil. 1H NMR (400 MHz, CDCl3): δ 1.95 (m, 1H), 2.20 (m, 2H), 2.45 (m, 1H), 3.68 (m, 2H), 3.96 (s, 3H, NCH3), 3.98 (s, 3H, OCH3), 4.22-4.24 (m, 1H), 4.38 (m, 1H), 4.61 (m, 1H), 7.01-7.28 (t, 1H, CHF2), 7.50 (s, 2H, Ar—H), 7.61 (s, 1H), 7.89 (s, 1H). MS [M+H]+ 361/363/365.

Workup

  1. customwas prepared in analogy
  2. customThe ice bath was removed
  3. customreaction mixture
  4. washThe reaction mixture was washed with 2M HCl (10 ml), 1M NaOH (10 ml) and saturated NaCl (30 ml)
  5. dry with materialdried over Na2SO4
  6. customAfter removal of the solvent
  7. customthe residue (0.20 g in the form of an oil) was purified by flash chromatography over silica gel (eluent:cyclohexane/ethyl acetate 1:1)

Sources & evidence

ORD record
ord-f4c514f1c7104867bfa06cca5a840af7
Source dataset
uspto-grants-2014_01
Patent number
US08623902B2

Reaction notes

Loading…