N-(5-Chloro-2-methylphenyl)piperazine → (R)-1-(3-(4-Bromo-phenyl)-1-[3-[4-(5-chloro-2-methyl-phenyl)-piperazin-1-yl]-2-hydroxy-propyl]-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl)-ethanone

HRID 746939Notes

Reaction equation

HRID 746939 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]3[CH2:13][N:14]([C:17](=[O:19])[CH3:18])[CH2:15][CH2:16][C:11]=3[N:10]([CH2:20][C@H:21]3[CH2:23][O:22]3)[N:9]=2)=[CH:4][CH:3]=1.[CH3:24][C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][C:26]=1[N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1>CCO.C(Cl)Cl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:12]3[CH2:13][N:14]([C:17](=[O:19])[CH3:18])[CH2:15][CH2:16][C:11]=3[N:10]([CH2:20][C@H:21]([OH:22])[CH2:23][N:35]3[CH2:34][CH2:33][N:32]([C:26]4[CH:27]=[C:28]([Cl:31])[CH:29]=[CH:30][C:25]=4[CH3:24])[CH2:37][CH2:36]3)[N:9]=2)=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 693767N-(5-Chloro-2-methylphenyl)piperazineHCID 86584816(S)-1-[3-(4-Bromo-phenyl)-1-oxiranylmethyl-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone

Product 1

HCID 10153173(R)-1-(3-(4-Bromo-phenyl)-1-[3-[4-(5-chloro-2-methyl-phenyl)-piperazin-1-yl]-2-hydroxy-propyl]-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl)-ethanoneYield 61%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
70 °C

Procedure

(S)-1-[3-(4-Bromo-phenyl)-1-oxiranylmethyl-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone (37 mg, 0.98 mmol) and 4-(2-methyl-5-chlorophenyl)piperazine (36 mg, 0.17 mmol) were combined in EtOH (0.4 mL) and heated to 70° C. After 18 h the mixture Was allowed to cool, diluted with CH2Cl2 and purified by preparative TLC (silica, 8% MeOH/CH2Cl2) to give 35 mg (61%) the title compound. HPLC (reverse phase conditions): tR=4.41 min. MS (electrospray): m/z calculated for C28H3435Cl79BrN5O2 [M++H], 586.16, found 586.2. 1H NMR (CDCl3, 400 MHz, a mixture of amide rotamers): 7.56 (d (partially obscured), J=8.5, Hz, 2H), 7.53 (s, 4H), 7.48 (d, J=8.5 Hz, 2H), 7.08 (br d, J=8.5 Hz, 1H), 6.95 (m, 2H), 4.85 and 4.73 (A and B of AB quartet, Jab=15.6 Hz, 1H), 4.62 (s, 1H), 4.20 (m, 2H), 4.04 (m, 2H), 3.90-3.71 (m, 2H), 2.92-2.53 (m, 11H), 2.21 (s, 1.5H), 2.16 (s, 1.5H).

Workup

  1. temperatureto cool
  2. custompurified by preparative TLC (silica, 8% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-b5a5065731944f5aad3c4a45bf944346
Source dataset
uspto-grants-2008_07
Patent number
US07393850B2

Reaction notes

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