(2S,5R)-4-{3-[1-(6-bromo-chroman-3-yl)-3-(3-chloro-4-fluoro-phenyl)-ureido]-propyl}-2,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester → (2R,5S)-1-(6-bromo-chroman-3-yl)-3-(3-chloro-4-fluoro-phenyl)-1-[3-(2,5-dimethyi-pipe razin-1-yl)-propyl]-urea

HRID 1986634Notes

Reaction equation

HRID 1986634 reaction equation
C(OC([N:8]1[CH2:13][C@@H:12]([CH3:14])[N:11]([CH2:15][CH2:16][CH2:17][N:18]([CH:30]2[CH2:39][C:38]3[C:33](=[CH:34][CH:35]=[C:36]([Br:40])[CH:37]=3)[O:32][CH2:31]2)[C:19]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([F:28])=[C:24]([Cl:29])[CH:23]=2)=[O:20])[CH2:10][C@@H:9]1[CH3:41])=O)(C)(C)C.C(O)(C(F)(F)F)=O.C(Cl)Cl>C1(C)C=CC=CC=1>[Br:40][C:36]1[CH:37]=[C:38]2[C:33](=[CH:34][CH:35]=1)[O:32][CH2:31][CH:30]([N:18]([CH2:17][CH2:16][CH2:15][N:11]1[CH2:10][C@H:9]([CH3:41])[NH:8][CH2:13][C@H:12]1[CH3:14])[C:19]([NH:21][C:22]1[CH:27]=[CH:26][C:25]([F:28])=[C:24]([Cl:29])[CH:23]=1)=[O:20])[CH2:39]2

Participants

4

Reactant 2

HCID 11527530(2S,5R)-4-{3-[1-(6-bromo-chroman-3-yl)-3-(3-chloro-4-fluoro-phenyl)-ureido]-propyl}-2,5-dimethyl-piperazine-1-carboxylic acid tert-butyl esterHCID 21863450Trifluoroacetic acid methylene chloride

Product 1

HCID 11570310(2R,5S)-1-(6-bromo-chroman-3-yl)-3-(3-chloro-4-fluoro-phenyl)-1-[3-(2,5-dimethyi-pipe razin-1-yl)-propyl]-ureaYield 96%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

(2S,5R)-4-{3-[1-(6-bromo-chroman-3-yl)-3-(3-chloro-4-fluoro-phenyl)-ureido]-propyl}-2,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester (0.053 g, 0.081 mmol) was treated with 20% TFA/CH2Cl2 (0.4 mL) at room temperature for 2 hours. The reaction mixture was diluted with toluene (4 mL) and concentrated in vacuo. Purification on reverse-phase HPLC gave 0.043 g (96%) of (2R,5S)-1-(6-bromo-chroman-3-yl)-3-(3-chloro-4-fluoro-phenyl)-1-[3-(2,5-dimethyi-pipe razin-1-yl)-propyl]-urea as a white solid. 1H NMR (300 MHz, CD3OD): □ 7.83 (dd, J=6.6, 2.4 Hz, 1H), 7.53 (m, 2H), 7.45 (dd, J=8.7, 2.4 Hz, 1H), 7.38 (t, J=9.0 Hz, 1H), 6.98 (d, J=9.0 Hz, 1H), 4.71 (m, 1H), 4.46 (m, 2H), 4.07 (m, 1H), 4.00-3.20 (m, 10H), 2.26 (m, 2H), 1.66 (d, J=6.2 Hz, 3H), 1.63 (d, J=6.6 Hz, 3H). MS-ESI: 553.0 (M+H+).

Workup

  1. concentrationconcentrated in vacuo
  2. customPurification on reverse-phase HPLC

Sources & evidence

ORD record
ord-bf84f0b69ff341339860801ff9544c83
Source dataset
uspto-grants-2009_06
Patent number
US07550467B2

Reaction notes

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