Benzoyl chloride → HCID 21963502, compound

HRID 2211920Notes

Reaction equation

HRID 2211920 reaction equation
Cl.[S:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[C:4]([N:11]2[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][C:19]3[CH:24]=[CH:23][C:22]([NH2:25])=[C:21]([CH3:26])[CH:20]=3)[CH2:13][CH2:12]2)=[N:3]1.C(N(CC)CC)C.[C:34]([Cl:42])(=[O:41])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>C1COCC1>[ClH:42].[S:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[C:4]([N:11]2[CH2:12][CH2:13][N:14]([CH2:17][CH2:18][C:19]3[CH:24]=[CH:23][C:22]([NH:25][C:34](=[O:41])[C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)=[C:21]([CH3:26])[CH:20]=3)[CH2:15][CH2:16]2)=[N:3]1

Participants

5

Reactant 3

HCID 7412Benzoyl chlorideHCID 8471TriethylamineHCID 21963230HCID 21963230, compound

Product 1

HCID 21963502HCID 21963502, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-[2-(4-benzo[d]isothiazol-3-yl-piperazin-1-yl)-ethyl]-2-methyl-phenylamine Hydrochloride (0.224 g, 0.6 mmol) in dry THF (30 mL) was added triethylamine (0.167 mL, 1.20 mmol), followed by dropwise addition of benzoyl chloride (0.07 mL, 0.6 mmol). The reaction was stirred vigorously under N2 blanket at room temperature for 2 h. The reaction was quenched with H2O (25 mL) and diluted with ethylacetate (25 mL). The layers were separated and the organics washed with 1 N HCl (20 mL), sat. Na2CO3 (20 mL), brine (20 mL), dried (MgSO4), and concentrated to a residue. After chromatographic purification (5% MeOH/CH2Cl2), N-{4-[2-(4-benzo[d]isothiazol-3-yl-piperazin-1-yl)-ethyl]-2-methyl-phenyl}-benzamide was precipitated as its hydrochloride salt from dioxane/HCl(gas) treatment (0.162 g, 0.355 mmol). Yield=59%. 100% purity at 254 nM; LCMS (APCI): 457.2 [M+H]+, 1H NMR (400 MHz, DMSO-d6) δ 10.81 (bs, 1H), 9.88 (s, 1H), 8.13 (d, J=8.36 Hz, 1H), 8.09 (d, J=8.36 Hz, 1H), 7.95 (d, J=8.36 Hz, 1H), 7.62–7.42 (m, 5H), 7.30 (d, J=8.02 Hz, 1H), 7.18 (s, 1H), 7.12 (d, J=8.02 Hz, 1H), 4.10 (bd, J=12.32 Hz, 2H), 3.68 (bd, J=12.32 Hz, 2H), 3.50–3.33 (m, 6H), 3.32 (s, H2O), 3.10–3.00 (m, 2H), 2.47 (DMSO), 2.21 (s, 3H).

Workup

  1. customThe reaction was quenched with H2O (25 mL)
  2. additiondiluted with ethylacetate (25 mL)
  3. customThe layers were separated
  4. washthe organics washed with 1 N HCl (20 mL), sat. Na2CO3 (20 mL), brine (20 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated to a residue
  7. customAfter chromatographic purification (5% MeOH/CH2Cl2), N-{4-[2-(4-benzo[d]isothiazol-3-yl-piperazin-1-yl)-ethyl]-2-methyl-phenyl}-benzamide
  8. customwas precipitated as its hydrochloride salt from dioxane/HCl(gas) treatment (0.162 g, 0.355 mmol)

Sources & evidence

ORD record
ord-5ff86a9c5ca7419ba7acb1d9a54e18c4
Source dataset
uspto-grants-2006_09
Patent number
US07101886B2

Reaction notes

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