1,2-Dichloroethane → HCID 44349222, compound

HRID 228137Notes

Reaction equation

HRID 228137 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@H:9]([C:14]([N:16]2[CH2:21][CH2:20][N:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[N:28]([CH2:33][CH:34]3[CH2:36][CH2:35]3)[S:29]([CH3:32])(=[O:31])=[O:30])[CH2:18][CH2:17]2)=[O:15])[CH2:10][C:11](O)=[O:12])=[CH:4][CH:3]=1.[N:37]1([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C@H:9]([C:14]([N:16]2[CH2:17][CH2:18][N:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[N:28]([CH2:33][CH:34]3[CH2:36][CH2:35]3)[S:29]([CH3:32])(=[O:31])=[O:30])[CH2:20][CH2:21]2)=[O:15])[CH2:10][C:11]([N:40]2[CH2:41][CH2:42][N:37]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:38][CH2:39]2)=[O:12])=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 143452tert-Butyl piperazine-1-carboxylateHCID 69075736HCID 69075736, compound

Product 1

HCID 44349222HCID 44349222, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (3S)-3-[(4-chlorophenyl)methyl]-4-(4-{2-[(cyclopropylmethyl)(methylsulfonyl)amino]phenyl}-piperazinyl)-4-oxobutanoic acid (Step 6) (0.63 g, 0.97 mmol), tert-butyl piperazinecarboxylate (0.272 g, 1.46 mmol), HOBt (0.131 g, 0.97 mmol) and TEA (0.135 mL, 0.97 mmol) in 10 mL of CH2Cl2 at 0° C. was added EDC (0.28 g, 1.46 mmol). The reaction was warmed to RT and stirred for 12 h. The reaction was quenched with satd. NaHCO3, and extracted with 50 mL of EtOAc. The organic phase was washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude compound was further purified by silica gel column chromatography (EtOAc) to afford tert-butyl 4-[(3S)-3-[(4-chlorophenyl)methyl]-4-(4-{2-[(cyclopropylmethyl)(methylsulfonyl)amino]-phenyl}piperazinyl)-4-oxobutanoyl]piperazinecarboxylate as a white foam (0.3 g). MS (ESI, pos. ion) m/z: 702.5 (M+1). Calc'd for C35H48ClN5O6S: 701.30. Anal. Calc'd for C35H48ClN5O6S.0.5H2O: C, 59.10; H, 6.94; N. 9.85; Cl, 4.98. Found: C, 59.32; H, 6.94; N, 9.81; Cl, 5.17.

Workup

  1. customThe reaction was quenched with satd
  2. extractionNaHCO3, and extracted with 50 mL of EtOAc
  3. washThe organic phase was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude compound was further purified by silica gel column chromatography (EtOAc)

Sources & evidence

ORD record
ord-cc98c89ebb2d43138af255a1be1ed6a1
Source dataset
uspto-grants-2009_07
Patent number
US07560460B2

Reaction notes

Loading…