Pyridine → 2-Chloro-4-fluoro-N-[3-(1-methyl-piperidin-4-ylsulfanyl)-phenyl]-benzamide hydrogen chloride salt

HRID 1822057Notes

Reaction equation

HRID 1822057 reaction equation
N1C=CC=CC=1.[CH3:7][N:8]1[CH2:13][CH2:12][CH:11]([S:14][C:15]2[CH:16]=[C:17]([NH2:21])[CH:18]=[CH:19][CH:20]=2)[CH2:10][CH2:9]1.[Cl:22][C:23]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:24]=1[C:25](Cl)=[O:26]>ClCCl>[ClH:22].[Cl:22][C:23]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:24]=1[C:25]([NH:21][C:17]1[CH:18]=[CH:19][CH:20]=[C:15]([S:14][CH:11]2[CH2:10][CH2:9][N:8]([CH3:7])[CH2:13][CH2:12]2)[CH:16]=1)=[O:26]

Participants

5

Reactant 3

HCID 1049PyridineHCID 27365462-Chloro-4-fluorobenzoyl chlorideHCID 450977713-[(1-Methyl-4-piperidinyl)sulfanyl]aniline

Product 1

HCID 690724312-Chloro-4-fluoro-N-[3-(1-methyl-piperidin-4-ylsulfanyl)-phenyl]-benzamide hydrogen chloride salt

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Combine pyridine (0.110 mL, 1.36 mmol), 3-(1-methyl-piperidin-4-ylsulfanyl)-phenylamine (preparation 76,151 mg, 0.679 mmol) in dichloromethane (6.5 mL) at 0° C. Stir and add 2-chloro-4-fluorobenzoyl chloride (0.105 mL, 0.815 mmol). Allow to warm to ambient temperature and stir. After 2 hr., dilute with dichloromethane (10 mL) and wash with sodium hydroxide (1N, 3×10 mL). Combine the organic layers, dry over sodium sulfate and concentrate under reduced pressure. Purification by flash chromatography, eluting with dichloromethane/ammonia (2.0 N in methanol) [20/1] to give the title compound as free base (184 mg, 72%). Dissolve the residue in diethyl ether and treat with ethereal hydrogen chloride (1.0 M). Triturate the resulting gum with ether to give the title compound as the hydrogen chloride salt. 1H NMR (free base, CDCl3): 8.37 (bs, 1H), 7.65 (s, 1H), 7.58 (t, J=6.8 Hz, 1H), 7.42 (d, J=7.7 Hz, 1H), 7.21 (t, J=7.8 Hz, 1H), 7.14-7.06 (m, 2H), 6.99-6.93 (m, 1H), 3.05 (bs, 1H), 2.71 (bd, J=11.5 Hz, 2H), 2.19 (s, 3H), 2.03-1.90 (m, 4H), 1.67-1.56 (m, 2H). 13C NMR (free base, CDCl3): 164.9, 162.2 (d, JC-F=167.7 Hz), 137.9, 135.8, 132.0, 131.7 (d, JC-F=8.6 Hz), 131.4, 129.3, 128.0, 123.0, 118.6, 117.5 (d, JC-F=25.0 Hz), 114.5 (d, JC-F=21.3 Hz), 54.9, 46.0, 43.6, 32.4.

Workup

  1. customat 0° C
  2. stirringstir
  3. washwash with sodium hydroxide (1N, 3×10 mL)
  4. dry with materialCombine the organic layers, dry over sodium sulfate
  5. concentrationconcentrate under reduced pressure
  6. customPurification by flash chromatography
  7. washeluting with dichloromethane/ammonia (2.0 N in methanol) [20/1]

Sources & evidence

ORD record
ord-70c28b2da06043b3adbbe5b52b66f96f
Source dataset
uspto-grants-2009_10
Patent number
US07608629B2

Reaction notes

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