1-Methylpiperazine → HCID 10460834, compound

HRID 853987Notes

Reaction equation

HRID 853987 reaction equation
Cl[CH2:2][C:3]([NH:5][C:6]1[CH:14]=[CH:13][C:12]([Cl:15])=[C:11]2[C:7]=1[C:8](=[O:33])[N:9]([C@@H:16]([C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[C:24]([O:30][CH2:31][CH3:32])[CH:23]=1)[CH2:17][S:18]([CH3:21])(=[O:20])=[O:19])[CH2:10]2)=[O:4].[CH3:34][N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1>CC#N>[Cl:15][C:12]1[CH:13]=[CH:14][C:6]([NH:5][C:3](=[O:4])[CH2:2][N:38]2[CH2:39][CH2:40][N:35]([CH3:34])[CH2:36][CH2:37]2)=[C:7]2[C:11]=1[CH2:10][N:9]([C@@H:16]([C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[C:24]([O:30][CH2:31][CH3:32])[CH:23]=1)[CH2:17][S:18]([CH3:21])(=[O:19])=[O:20])[C:8]2=[O:33]

Participants

4

Reactant 2

HCID 531671-MethylpiperazineHCID 68690088(1S)-2-chloro-N-{7-chloro-2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-acetamide

Product 1

HCID 10460834HCID 10460834, compoundYield 25.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of (1S)-2-chloro-N-{7-chloro-2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-acetamide (250 mg, 0.48 mmol) in CH3CN (10 ml) was added 1-methylpiperazine (0.21 ml, 1.9 mmol). The mixture was heated at 70° C. for 2 hrs. The reaction mixture was concentrated on rota-vap and extracted with water (50 ml) and EtOAc (50 ml). The organic layer was washed with water (50 ml), brine (25 ml), dried over Na2SO4 and concentrated. The resulted oil was purified by chromatography to give (1S)-N-{7-chloro-2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-2-(4-methyl-piperazin-1-yl)-acetamide as a white solid (70 mg, 25% yield): mp, 205-207° C.; 1H NMR (CDCl3) δ 1.47 (t, J=7.0 Hz, 3H, OCH2CH3), 2.36 (s, 3H, CH3), 2.64 (broad, 8H, CH2 on piperazine ring), 2.99 (S, 3H, NCH3), 3.21 (d, J=2 Hz, 2H, CH2NCO), 3.73 (dd, J=5, 15 Hz, 1H, CHHSO2), 3.88 (s, 3H, OCH3), 4.05-4.20 (m, 4H, CHHSO2+CNHH+OCH2CH3), 4.39 (d, J=15 Hz, 1H, CHHN), 5.74-5.80 (m, 1H, NCH), 6.86-6.98 (m, 3H, Ar), 7.40 (d, J=8 Hz, 1H, Ar), 8.55 (d, J=8 Hz, 1H, Ar), 11.45 (s, 1H, NHCO); 13C NMR (CDCl3) δ 14.73, 41.37, 46.11, 46.81, 51.57, 53.46, 54.81, 55.76, 55.98, 62.18, 64.62, 111.61, 112.42, 119.46, 119.77, 119.87, 122.32, 129.20, 132.95, 135.98, 139.21, 148.93, 149.87, 168.50, 170.01. Anal Calcd for C27H35ClN4O6S: C, 56.00; H, 6.09; N, 9.67. Found: C, 55.82; H, 5.79; N, 9.42.

Workup

  1. concentrationThe reaction mixture was concentrated on rota-vap
  2. extractionextracted with water (50 ml) and EtOAc (50 ml)
  3. washThe organic layer was washed with water (50 ml), brine (25 ml)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe resulted oil was purified by chromatography

Sources & evidence

ORD record
ord-f1357eb3987f4ae8bca9d18d2a51b2ca
Source dataset
uspto-grants-2007_08
Patent number
US07256210B2

Reaction notes

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