1,2-Dichloroethane → HCID 69078832, compound

HRID 228131Notes

Reaction equation

HRID 228131 reaction equation
[CH:1]1([CH2:4][N:5]([S:18]([CH3:21])(=[O:20])=[O:19])[C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=2[N:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)[CH2:3][CH2:2]1.[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29][C@H:30]([OH:34])[C:31](O)=[O:32])=[CH:25][CH:24]=1.C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl>C(Cl)Cl.CN(C=O)C>[Cl:22][C:23]1[CH:24]=[CH:25][C:26]([CH2:29][C@H:30]([OH:34])[C:31]([N:15]2[CH2:16][CH2:17][N:12]([C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=3[N:5]([CH2:4][CH:1]3[CH2:2][CH2:3]3)[S:18]([CH3:21])(=[O:19])=[O:20])[CH2:13][CH2:14]2)=[O:32])=[CH:27][CH:28]=1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 181649HOAtHCID 11183257HCID 11183257, compoundHCID 58996660HCID 58996660, compound

Product 1

HCID 69078832HCID 69078832, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a 250-mL round bottomed-flask equipped with a magnetic stir bar and containing a solution of N-(cyclopropylmethyl)(methylsulfonyl)(2-piperazinyl-phenyl)amine (Step 2) (1.8 g, 5.8 mmol) and (2S)-3-(4-chlorophenyl)-2-hydroxypropanoic acid (Step 1) (1.2 g, 5.8 mmol) in CH2Cl2 (30 mL) and DMF (30 mL) at RT was added HOAT (Aldrich) (0.87 g, 6.4 mmol) followed by EDC (Aldrich) (1.3 g, 7.0 mmol). This was stirred for 18 h and diluted with CH2Cl2 (300 mL). The mixture was washed with H2O (3×100 mL), aq. NaHCO3 (1×100 mL) and brine (1×100 mL). It was dried (Na2SO4) and concentrated onto silica gel. Purification by chromatography (40 to 55% EtOAc/hexanes) afforded (2S)-3-(4-chlorophenyl)-1-(4-{2-[(cyclopropylmethyl)-(methylsulfonyl)amino]-phenyl}-piperazinyl)-2-hydroxypropan-1-one as a slightly yellow oil (1.8 g). Analytically pure material was obtained by reverse phase preparative scale chromatography (Column: MetaChem Polaris C18-A 5 micron, flow: 20 mL/min, gradient: 5 to 100% CH3CN (0.1% TFA)/H2O (0.1% TFA). MS (ESI, pos. ion) m/z 492 (M+1). Calc'd for C24H30ClN3O4S: 491.16.

Workup

  1. customTo a 250-mL round bottomed-flask equipped with a magnetic stir bar
  2. washThe mixture was washed with H2O (3×100 mL), aq. NaHCO3 (1×100 mL) and brine (1×100 mL)
  3. dry with materialIt was dried (Na2SO4)
  4. concentrationconcentrated onto silica gel
  5. customPurification by chromatography (40 to 55% EtOAc/hexanes)

Sources & evidence

ORD record
ord-ba96f7e8beb04463aedb61a2abdaf17c
Source dataset
uspto-grants-2009_07
Patent number
US07560460B2

Reaction notes

Loading…