Hydrochloric Acid → HCID 18758331, compound

HRID 1661753Notes

Reaction equation

HRID 1661753 reaction equation
[Cl:1][CH2:2][C:3]([NH:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[C:8](=[O:32])[N:9]([CH:16]([C:21]1[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[C:23]([O:29][CH2:30][CH3:31])[CH:22]=1)[CH2:17][C:18](=[O:20])[CH3:19])[C:10]2=[O:15])=[O:4].[CH3:33][NH:34][CH3:35].Cl>O1CCCC1.C(OCC)(=O)C.CCOCC>[ClH:1].[CH3:33][N:34]([CH3:35])[CH2:2][C:3]([NH:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[C:8](=[O:32])[N:9]([CH:16]([C:21]1[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[C:23]([O:29][CH2:30][CH3:31])[CH:22]=1)[CH2:17][C:18](=[O:20])[CH3:19])[C:10]2=[O:15])=[O:4]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 674DimethylamineHCID 12110005HCID 12110005, compound

Product 1

HCID 18758331HCID 18758331, compoundYield 44.1%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 2-chloro-N-{2-[1-(3-ethoxy-4-methoxyphenyl)-3-oxobutyl]-1,3-dioxoisoindolin-4-yl}acetamide (1.07 g, 2.34 mmol) and N,N-dimethylamine (2.0 M in methanol, 3.5 mL, 7.0 mmol) in tetrahydrofuran (15 mL) was stirred at room temperature for 16 hours. The solvent was removed in vacuo to give an oil. The oil was purified by chromatography (silica gel, methylene chloride:ethyl acetate 7:3) to give a white solid. To a solution of the solid in ethyl acetate (10 mL) was added hydrogen chloride in ether (1N, 4 mL). The slurry was filtered and washed with ether to give 2-(dimethylamino)-N-{2-[1-(3-ethoxy-4-methoxyphenyl)-3-oxobutyl]-1,3-dioxoisoindolin-4-yl}acetamide hydrochloride as a white solid (0.52 g, 44%); mp 100-102° C.; 1H NMR (DMSO-d6) δ 10.63 (s, 1H), 10.27 (s, 1H), 8.21 (d, J=8.2 Hz, 1H), 7.84 (t, J=7.7 Hz, 1H), 7.67 (d, J=7.3 Hz, 1H), 6.98 (s, 1H), 6.89 (s, 2H), 5.63-5.57 (dd, J=6.0 and 8.8 Hz, 1H), 4.19 (b, 2H), 3.99 (q, J=6.9 Hz, 2H), 3.77-3.67 (m, 1H), 3.74 (s, 3H), 3.52-3.42 (dd, J=6.1 and 18.1 Hz, 1H), 2.84 (s, 6H), 2.12 (s, 3H), 1.30 (t, J=6.9 Hz, 3H); 13C NMR (DMSO-d6) δ 205.81, 167.32, 167.14, 164.84, 148.49, 147.76, 135.85, 134.29, 131.74, 131.48, 127.70, 119.48, 119.27, 119.09, 112.19, 111.76, 63.76, 58.32, 55.48, 48.90, 44.27, 43.47, 29.87, 14.69; Anal. Calcd. For C26H30N3O6Cl: C, 59.58; H, 6.00; N, 8.34; Cl, 7.03. Found: C, 59.18; H, 6.03; N, 8.14; Cl, 6.68.

Workup

  1. customThe solvent was removed in vacuo
  2. customto give an oil
  3. customThe oil was purified by chromatography (silica gel, methylene chloride:ethyl acetate 7:3)
  4. customto give a white solid
  5. filtrationThe slurry was filtered
  6. washwashed with ether

Sources & evidence

ORD record
ord-e3ee8e8917104fd3b541455de211ac03
Source dataset
uspto-grants-2011_10
Patent number
US08030343B2

Reaction notes

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