4-(Methylthio)aniline → HCID 57489635, compound

HRID 2044084Notes

Reaction equation

HRID 2044084 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Cl[C:12]1[N:20]=[C:19]([Cl:21])[CH:18]=[CH:17][C:13]=1[C:14]([NH2:16])=[O:15].[CH3:22][S:23][C:24]1[CH:30]=[CH:29][C:27]([NH2:28])=[CH:26][CH:25]=1>C1COCC1>[Cl:21][C:19]1[CH:18]=[CH:17][C:13]([C:14]([NH2:16])=[O:15])=[C:12]([NH:28][C:27]2[CH:29]=[CH:30][C:24]([S:23][CH3:22])=[CH:25][CH:26]=2)[N:20]=1

Participants

5

Reactant 3

HCID 660384-(Methylthio)anilineHCID 2733832Lithium HexamethyldisilazideHCID 221427782,6-Dichloropyridine-3-carboxamide

Product 1

HCID 57489635HCID 57489635, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A 1 M THF solution of LiHMDS (6.06 mL, 6.06 mmol) was added dropwise to a mixture of 2,6-dichloronicotinamide (331 mg, 1.733 mmol) and 4-(methylthio)aniline (289 mg, 2.079 mmol) in THF (20 mL) at 0° C. The resulting brown solution was stirred at 0° C. for 5 min, at room temperature for 30 min, quenched with saturated NH4Cl (50 mL) and extracted with EtOAc (3×25 mL). The combined extracts were washed with brine (5 mL), dried (MgSO4), and concentrated. Silica gel chromatography, eluting with 30-70% EtOAc in hexanes, gave the desired product as tan solid (376 mg, 74% yield). LCMS: (M+H)+=293.9. 1H NMR (400 MHz, chloroform-d) δ ppm 10.74 (1H, s), 7.54-7.73 (3H, m), 7.20-7.36 (2H, m), 6.68 (1H, d, J=8.03 Hz), 5.84 (2H, br. s.), 2.48 (3H, s).

Workup

  1. customquenched with saturated NH4Cl (50 mL)
  2. extractionextracted with EtOAc (3×25 mL)
  3. washThe combined extracts were washed with brine (5 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. washSilica gel chromatography, eluting with 30-70% EtOAc in hexanes

Sources & evidence

ORD record
ord-38bcbe3955564b2d956d0336b2eede16
Source dataset
uspto-grants-2013_11
Patent number
US08586751B2

Reaction notes

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