3-Chloro-4-fluorophenyl isocyanate → (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

HRID 1986633Notes

Reaction equation

HRID 1986633 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][C@@H:12]([CH3:14])[N:11]([CH2:15][CH2:16][CH2:17][NH:18][CH:19]2[CH2:28][C:27]3[C:22](=[CH:23][CH:24]=[C:25]([Br:29])[CH:26]=3)[O:21][CH2:20]2)[CH2:10][C@@H:9]1[CH3:30])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:31][C:32]1[CH:33]=[C:34]([N:39]=[C:40]=[O:41])[CH:35]=[CH:36][C:37]=1[F:38]>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][C@@H:12]([CH3:14])[N:11]([CH2:15][CH2:16][CH2:17][N:18]([CH:19]2[CH2:28][C:27]3[C:22](=[CH:23][CH:24]=[C:25]([Br:29])[CH:26]=3)[O:21][CH2:20]2)[C:40]([NH:39][C:34]2[CH:35]=[CH:36][C:37]([F:38])=[C:32]([Cl:31])[CH:33]=2)=[O:41])[CH2:10][C@@H:9]1[CH3:30])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 2

HCID 27346323-Chloro-4-fluorophenyl isocyanateHCID 68866043(2S,5R)-4-[3-(6-bromo-chroman-3-ylamino)-propyl]-2,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester

Product 1

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 esterYield 29%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (2S,5R)-4-[3-(6-bromo-chroman-3-ylamino)-propyl]-2,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester (0.12 g, 0.25 mmol) in CH2Cl2 (0.5 mL) was added 3-chloro-4-fluoro-phenylisocyanate (0.043 g, 0.25 mmol). After stirring at room temperature for 16 hours, the mixture was concentrated in vacuo and the residue was purified on reverse-phase HPLC to give 0.047 g (29%) of (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 as a white solid. 1H NMR (300 MHz, CDCl3): δ 7.85 (d, J=17.4 Hz, 1H), 7.62 (d, J=6.3 Hz, 1H), 7.23 (m, 2H), 7.02 (t, J=9.0 Hz, 1H), 6.71 (d, J=9.0 Hz, 1H), 6.14 (br.s, 1H), 4.55 (m, 2H), 4.26 (m, 2H), 3.92 (m, 1H), 3.60-2.70 (m, 10H), 2.05 (m, 2H), 1.46 (s, 9H), 1.37 (d, J=7.2 Hz, 3H), 1.20 (m, 3H). MS-ESI: 653.1 (M+H+).

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. customthe residue was purified on reverse-phase HPLC

Sources & evidence

ORD record
ord-9983926678734a50940bf9036a1423c6
Source dataset
uspto-grants-2009_06
Patent number
US07550467B2

Reaction notes

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