Hydrochloric Acid → HCID 10370561, compound

HRID 1797259Notes

Reaction equation

HRID 1797259 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][NH:35][CH3:36].Cl>CC#N.CCOCC>[Cl:15][C:12]1[CH:13]=[CH:14][C:6]([NH:5][C:3](=[O:4])[CH2:2][N:35]([CH3:36])[CH3:34])=[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

6

Reactant 3

HCID 313Hydrochloric AcidHCID 674DimethylamineHCID 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 10370561HCID 10370561, 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 (400 mg, 0.78 mmol) in CH3CN (10 ml) was added dimethylamine (2N in MeOH, 1.6 ml, 3.2 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-dimethylamino-acetamide; hydrochloride as a white solid (300 mg, 68% yield): mp, 198–200° C.; 1H NMR (DMSO-d6) δ 1.32 (t, J=7.5 Hz, 3H, OCH2CH3), 2.87 (s, 6H, N(CH3)2), 3.04 (s, 3H, CH3), 3.74 (s, 3H, CH3), 3.94–4.16 (m, 4H, OCH2CH3+NCHH+CHHSO2), 4.36–4.50 (m, 3H, CHHSO2+CH2NCO), 4.73 (d, J=18 Hz, 1H, CHHN), 5.85–5.91 (m, 1H, NCH), 6.98 (s, 2H, Ar), 7.05 (s, 1H, Ar), 7.69 (d, J=8 Hz, 1H, Ar), 8.18 (d, J=8 Hz, 1H, Ar), 10.21 (bs, 1H, HCl); 10.45 (s, 1H, NHCO); 13C NMR (DMSO-d6) δ 15.17, 23.25, 41.51, 43.86, 46.03, 49.41, 53.88, 56.00, 58.52, 64.41, 112.50, 112.80, 120.23, 121.25, 123.33, 130.22, 133.21, 134.72, 140.60, 148.55, 149.46, 154.53, 167.02, 180.13. Anal Calcd for C24H31Cl2N3O6S+0.41 H2O: C, 50.78; H, 5.65; N, 7.40. Found: C, 50.81; H, 5.55; N, 7.18; H2O, 1.30.

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-b39f141b0a0842128d5be8abc2a8a882
Source dataset
uspto-grants-2006_04
Patent number
US07034052B2

Reaction notes

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