1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-(4-fluorophenyl)-5-methoxy-N-methylbenzo[b]thiophene-3-carboxamide

HRID 44026Notes

Reaction equation

HRID 44026 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]3[CH:13]=[CH:14][C:15]([O:17][CH3:18])=[CH:16][C:10]=3[C:9]=2[C:19]([OH:21])=O)=[CH:4][CH:3]=1.C1C=[N:26][C:25]2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.Cl.CN.CCN=C=NCCCN(C)C>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]3[CH:13]=[CH:14][C:15]([O:17][CH3:18])=[CH:16][C:10]=3[C:9]=2[C:19]([NH:26][CH3:25])=[O:21])=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 6364545Methylamine hydrochlorideHCID 59233734HCID 59233734, compound

Product 1

HCID 592337112-(4-fluorophenyl)-5-methoxy-N-methylbenzo[b]thiophene-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution containing 2-(4-fluorophenyl)-5-methoxybenzo[b]thiophene-3-carboxylic acid (0.57 g, 1.9 mmol), HOAT (0.28 g, 2.1 mmol), diisopropylethylamine (2.3 mL, 13.2 mmol), methylamine hydrochloride (0.20 g, 2.8 mmol) and dichloromethane (20 mL) was added EDCI (0.51 g, 13.2 mmol). The solution was maintained at room temperature for 6 h, diluted with additional DCM (20 mL), washed with water (20 mL), washed with aqueous HCl (2×20 mL, 0.1N), dried over MgSO4, filtered and concentrated to afford 2-(4-fluorophenyl)-5-methoxy-N-methylbenzo[b]thiophene-3-carboxamide which was used without further purification. 1H NMR (500 MHz, DMSO-D6) δ ppm 8.30 (d, J=4.27 Hz, 1H), 7.90 (d, J=8.85 Hz, 1H), 7.60 (dd, J=8.70, 5.34 Hz, 2H), 7.34 (t, J=8.85 Hz, 2H), 7.16 (d, J=2.14 Hz, 1H), 7.07 (dd, J=8.85, 2.44 Hz, 1H), 3.81 (s, 3H), 2.74 (d, J=4.58 Hz, 3H). LCMS: retention time: 2.513 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna, 10 micron, C18, 4.6×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 4 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 4 min, a hold time of 1 min, and an analysis time of 5 min where solvent A was 5% CH3CN/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% CH3CN/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 316 (MH+).

Workup

  1. washwashed with water (20 mL)
  2. washwashed with aqueous HCl (2×20 mL, 0.1N)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-eae3144cb8284245adceb8e8cf169b17
Source dataset
uspto-grants-2013_09
Patent number
US08536338B2

Reaction notes

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