Methanamine, N-methoxy-, hydrochloride (1:1) → 2-(2,4-dichloro-benzenesulfonylamino)-N-methoxy-N-methyl-5-[4-(piperidine-1-sulfonyl)-phenylsulfanyl]-isonicotinamide

HRID 1366856Notes

Reaction equation

HRID 1366856 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[S:9]([NH:12][C:13]1[CH:14]=[C:15]([C:19]([S:22][C:23]2[CH:28]=[CH:27][C:26]([S:29]([N:32]3[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]3)(=[O:31])=[O:30])=[CH:25][CH:24]=2)=[CH:20][N:21]=1)[C:16](O)=[O:17])(=[O:11])=[O:10].Cl.[CH3:39][NH:40][O:41][CH3:42].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[S:9]([NH:12][C:13]1[CH:14]=[C:15]([C:19]([S:22][C:23]2[CH:28]=[CH:27][C:26]([S:29]([N:32]3[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]3)(=[O:30])=[O:31])=[CH:25][CH:24]=2)=[CH:20][N:21]=1)[C:16]([N:40]([O:41][CH3:42])[CH3:39])=[O:17])(=[O:11])=[O:10]

Participants

7

Reactant 4

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 577182032-(2,4-Dichloro-benzenesulfonylamino)-5-[4-(piperidine-1-sulfonyl)-phenylsulfanyl]-isonicotinic acid

Product 1

HCID 577181912-(2,4-dichloro-benzenesulfonylamino)-N-methoxy-N-methyl-5-[4-(piperidine-1-sulfonyl)-phenylsulfanyl]-isonicotinamideYield 82%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2-(2,4-dichloro-benzenesulfonylamino)-5-[4-(piperidine-1-sulfonyl)-phenylsulfanyl]-isonicotinic acid (173 mg, 0.29 mmol), N,O-dimethylhydroxylamine hydrochloride (84 mg, 0.86 mmol), TBTU (276 mg, 0.86 mmol) and DIPEA (0.18 ml, 1 mmol) in DMF (10 ml) was stirred at room temperature overnight under nitrogen. The reaction was diluted with ethyl acetate (25 ml), washed with brine (3×25 ml), dried (MgSO4) and concentrated under reduced pressure. The residue was purified by flash column chromatography using methanol 1/9 chloroform as eluent to afford 2-(2,4-dichloro-benzenesulfonylamino)-N-methoxy-N-methyl-5-[4-(piperidine-1-sulfonyl)-phenylsulfanyl]-isonicotinamide as a yellow oil (153 mg, 82%). 1H NMR (CDCl3): 8.40 (1 H, s, Ar); 8.07 (1 H, d, Ar); 7.53 (2 H, d, Ar); 7.46 (1 H, s, py); 7.34 (1 H, d, Ar); 7.22 (3 H, m, py and Ar); 3.34 (3 H, s, CH3O); 3.24 (3 H, s, CH3N); 2.88 (4 H, m, 2×CH2N pip); 1.55 (4 H, m, 2×CH2 pip); 1.33 (2 H, m, CH2 pip).

Workup

  1. washwashed with brine (3×25 ml)
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-f1dce4763de6467ba2ad84277266d11c
Source dataset
uspto-grants-2011_02
Patent number
US07893077B2

Reaction notes

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