Acetyl chloride → HCID 11705135, compound

HRID 729292Notes

Reaction equation

HRID 729292 reaction equation
[C:1](Cl)(=[O:3])[CH3:2].[CH2:5]([N:9]1[C:13](=[O:14])[C:12]([NH:15][C:16]2[CH:17]=[C:18]3[C:23](=[CH:24][CH:25]=2)[CH2:22][NH:21][CH2:20][CH2:19]3)=[C:11]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[S:10]1(=[O:33])=[O:32])[CH2:6][CH2:7][CH3:8].CCOC(C)=O>C1COCC1>[C:1]([N:21]1[CH2:20][CH2:19][C:18]2[C:23](=[CH:24][CH:25]=[C:16]([NH:15][C:12]3[C:13](=[O:14])[N:9]([CH2:5][CH2:6][CH2:7][CH3:8])[S:10](=[O:32])(=[O:33])[C:11]=3[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH:17]=2)[CH2:22]1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 8857Ethyl AcetateHCID 115967233(2H)-Isothiazolone, 2-butyl-5-phenyl-4-[(1,2,3,4-tetrahydro-6-isoquinolinyl)amino]-, 1,1-dioxide

Product 1

HCID 11705135HCID 11705135, compoundYield 64.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Acetyl chloride (0.020 ml, 0.243 mmol) was added to a solution of 2-butyl-5-phenyl-4-(1,2,3,4-tetrahydroisoquinolin-6-ylamino)isothiazol-3(2H)-one 1,1-dioxide (example 60) (0.100 g, 0.243 mmol) and TEA (0.040 mmol, 0.267 mmol) in dry THF (2 ml) and the reaction mixture was stirred at rt for 40 mins. EtOAc was added and the mixture was washed with brine and evaporated. The residue was purified by silica gel column chromatography using a 1:5 mixture of EtOAc/petroleum ether 40-60° C. mixture as eluent, to give the title compound (0.071 g, 64%). 1H NMR (500 MHz CDCl3); δ 7.30-7.22 (m, 2H), 7.22-7.14 (m, 4H), 6.88, 6.68 (dd, 1H), 6.68 (td, 1H), 6.36, 6.31 (d, 1H), 4.58, 4.47 (s, 2H), 3.79 (t, 2H), 3.63, 3.48 (t, 2H), 2.43, 2.39 (t, 2H), 2.16, 2.15 (s, 3H), 1.94-1.84 (m, 2H), 1.56-1.44 (m, 2H), 1.01 (t, 3H); 13C NMR (125 MHz CDCl3): δ 169.8, 159.6, 135.8, 134.4, 131.0, 130.8, 129.6, 129.4, 128.3, 127.0, 126.2, 126.0, 122.6, 122.2, 120.4, 120.0, 111.4, 111.2, 47.8, 43.9, 40.5, 39.4, 30.5, 29.3, 26.8, 22.0, 21.8, 20.3, 13.8; Mass Spectrum M+H+ 454.

Workup

  1. washthe mixture was washed with brine
  2. customevaporated
  3. customThe residue was purified by silica gel column chromatography
  4. additiona 1:5 mixture of EtOAc/petroleum ether 40-60° C. mixture as eluent

Sources & evidence

ORD record
ord-db27ea2d4af6483097f94a942ae4a449
Source dataset
uspto-grants-2009_09
Patent number
US07582629B2

Reaction notes

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