Hydrochloric Acid → AV-608

HRID 1738914Notes

Reaction equation

HRID 1738914 reaction equation
[F:1][C:2]([F:31])([F:30])[C:3]1[CH:4]=[C:5]([CH:23]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:25]=1)[C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([NH2:14])[CH2:10][C@H:9]1[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=1)=[O:7].C(N(CC)CC)C.Cl.[N:40]1[C:49]2[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=2)[C:43]([C:50](Cl)=[O:51])=[CH:42][CH:41]=1.Cl>C(Cl)Cl>[F:31][C:2]([F:1])([F:30])[C:3]1[CH:4]=[C:5]([CH:23]=[C:24]([C:26]([F:27])([F:28])[F:29])[CH:25]=1)[C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([NH:14][C:50]([C:43]2[C:44]3[C:49](=[CH:48][CH:47]=[CH:46][CH:45]=3)[N:40]=[CH:41][CH:42]=2)=[O:51])[CH2:10][C@H:9]1[CH2:15][C:16]1[CH:17]=[CH:18][C:19]([Cl:22])=[CH:20][CH:21]=1)=[O:7]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8471Triethylamine2×HCID 12373997Quinoline-4-carbonyl chloride hydrochloride2×HCID 22869970HCID 22869970, compound

Product 1

HCID 9917079AV-608

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 1.70 g (3.65 mmol) of (2R,4S)-1-(3,5-bis-trifluoromethyl-benzoyl)-2-(4-chloro-benzyl)-piperidine4-amine and 1.5 ml (10.96 mmol) of triethylamine in 3 ml of methylene chloride is added dropwise at 0° C. to a solution of 0.915 g (4.01 mmol) of quinoline4-carboxylic acid chloride hydrochloride [Nicolai E, Gungor T, Goyard J, Cure G, Fouquet A, Teulon J M, Delchambre C, Cloarec A, Eur. J. Med. Chem., 1992, 27, 977] in 10 ml of methylene chloride. After 15 hours, a further 228 mg (1.0 mmol) of quinoline-4-carboxylic acid chloride hydrochloride and a further 0.1 ml (1.0 mmol) of triethylamine are added and the mixture is stirred for 3 hours. 1 N hydrochloric acid is added to the mixture which is then extracted with ethyl acetate. The organic phase is washed with 1 N sodium hydroxide solution and with brine, dried over sodium sulfate and concentrated. The residue is crystallised from toluene and yields the title compound in the form of white crystals. M.p. 204-207° C. (phase transition 135-140° C.); TLC: ethyl acetate: Rf =0.48, FD-MS: M+ =619(621). ##STR17##

Workup

  1. extractionis then extracted with ethyl acetate
  2. washThe organic phase is washed with 1 N sodium hydroxide solution and with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue is crystallised from toluene

Sources & evidence

ORD record
ord-a3fcaa192e8547f29980b83a61e3ae05
Source dataset
uspto-grants-1999_10
Patent number
US05965562

Reaction notes

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