2-Chloro-4'-fluoroacetophenone → (S)-1-[3-ethyl-5-(1-methyl-1H-tetrazol-5-yl)-phenyl]-3-{1-[2-(4-fluorophenyl)-2-oxo-ethyl]-piperidin-3-ylmethyl}-urea

HRID 896561Notes

Reaction equation

HRID 896561 reaction equation
Cl.[CH2:2]([C:4]1[CH:5]=[C:6]([NH:16][C:17]([NH:19][CH2:20][C@H:21]2[CH2:26][CH2:25][CH2:24][NH:23][CH2:22]2)=[O:18])[CH:7]=[C:8]([C:10]2[N:14]([CH3:15])[N:13]=[N:12][N:11]=2)[CH:9]=1)[CH3:3].Cl[CH2:28][C:29]([C:31]1[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=1)=[O:30]>C(N(CC)CC)C>[CH2:2]([C:4]1[CH:5]=[C:6]([NH:16][C:17]([NH:19][CH2:20][C@@H:21]2[CH2:26][CH2:25][CH2:24][N:23]([CH2:28][C:29]([C:31]3[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=3)=[O:30])[CH2:22]2)=[O:18])[CH:7]=[C:8]([C:10]2[N:14]([CH3:15])[N:13]=[N:12][N:11]=2)[CH:9]=1)[CH3:3]

Participants

4

Reactant 2

HCID 1202482-Chloro-4'-fluoroacetophenone2×HCID 20814990(S)-1-[3-Ethyl-5-(1-methyl-1H-tetrazol-5-yl)-phenyl]-3-piperidin-3-ylmethyl-urea Hydrochloride

Product 1

HCID 69736343(S)-1-[3-ethyl-5-(1-methyl-1H-tetrazol-5-yl)-phenyl]-3-{1-[2-(4-fluorophenyl)-2-oxo-ethyl]-piperidin-3-ylmethyl}-ureaYield 81%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

A solution of (S)-1-[3-ethyl-5-(1-methyl-1H-tetrazol-5-yl)-phenyl]-3-piperidin-3-ylmethyl-ureahydrochloride (50 with 2-chloro-4′-fluoroacetophenone (27 mg, 158 μmol) and minutes. Additional triethylamine (73 μL, 526 μμmol) and 2-chloro-4′-fluoroacetophenone (ca. 5 mg) were added and stirring was continued for 60 minutes more. The mixture was concentrated under vacuum, and the residue was purified by flash chromatography, eluting with 3% methanol in dichloromethane, containing 0.3% aqueous ammonia, to provide a tan glassy solid (51 mg, 81%). 1H NMR (300 MHz, CDCl3) δ8.02 (m, 3H), 7.70 (s, 1H), 7.59 (s, 1H), 7.13 (m, 3H), 6.64 (bs, 1H), 4.20 (s, 3H), 3.85 (ab, J=18 Hz, 2H), 3.30 (m, 2H), 2.9-2.6 (m, 4H), 2.37 (m, 2H), 2.0-1.6 (m, 5H), 1.25 (t, J=8 Hz, 3H). Mass spec (ES+) m/z 480.4 (M+H+).

Workup

  1. concentrationThe mixture was concentrated under vacuum
  2. customthe residue was purified by flash chromatography
  3. washeluting with 3% methanol in dichloromethane
  4. additioncontaining 0.3% aqueous ammonia

Sources & evidence

ORD record
ord-fea71cf6043a48bab095d1585f04a95a
Source dataset
uspto-grants-2005_07
Patent number
US06919356B2

Reaction notes

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