Hydrochloric Acid → HCID 10326267, compound

HRID 1797258Notes

Reaction equation

HRID 1797258 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].[NH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1.Cl>CC#N.CCOCC>[Cl:15][C:12]1[CH:13]=[CH:14][C:6]([NH:5][C:3](=[O:4])[CH2:2][N:34]2[CH2:39][CH2:38][O:37][CH2:36][CH2:35]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:20])=[O:19])[C:8]2=[O:33]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 8083MorpholineHCID 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 10326267HCID 10326267, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 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 morpholine (0.17 ml, 1.94 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 an oil which was stirred with HCl in ether (3 ml) 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-morpholin-4-yl-acetamide; hydrochloride as a white solid (200 mg, 68% yield): mp, 198–200° C.; 1H NMR (CDCl3 with D2O added) δ 1.46 (t, J=7.0 Hz, 3H, OCH2CH3), 2.68 (broad, 4H, CH2NCH2 on morpholino ring), 2.99 (s, 3H, SCH3), 3.24 (broad, 2H, CH2NCO), 3.72 (dd, J=5, 15 Hz, 1H, CHHSO2), 3.87–3.92 (m, 7H, OCH3+CH2OCH2 on morpholine ring), 4.05–4.23 (m, 4H, CHHSO2+CNHH+OCH2CH3), 4.40 (d, J=15 Hz, 1H, CHHN), 5.71–5.77 (m, 1H, NCH), 6.86–6.97 (m, 3H, Ar), 7.40 (d, J=8 Hz, 1H, Ar), 8.52 (d, J=8 Hz, 1H, Ar); 13C NMR (CDCl3) δ 14.75, 41.71, 47.09, 51.22, 51.59, 55.09, 56.02, 63.81, 64.10, 64.81, 105.68, 111.67, 112.28, 119.32, 120.0, 120.27, 124.03, 128.81, 133.20, 134.72, 139.41, 149.09, 150.01, 168.55. Anal Calcd for C26H33Cl2N3O7S+0.53 H2O: C, 51.02; H, 5.61; N, 6.87. Found: C, 50.70; H, 5.38; N, 6.76, 0.98% H2O.

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
  7. customto give an oil which

Sources & evidence

ORD record
ord-57b810afcf7041a48f180ff2cfcf1901
Source dataset
uspto-grants-2006_04
Patent number
US07034052B2

Reaction notes

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