Dimethylamine → N-[2-(5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenylcarbamoyl)-benzo[b]thiophen-7-yl]-5-(N,N-dimethylcarbamoyl)-nicotinamide

HRID 1986660Notes

Reaction equation

HRID 1986660 reaction equation
[N:1]1[CH:6]=[C:5]([C:7]([OH:9])=O)[CH:4]=[C:3]([C:10]([OH:12])=O)[CH:2]=1.[CH2:13]([N:15](CC)[CH2:16]C)C.[C:20]([C:24]1[CH:25]=[C:26]([NH:45][S:46]([CH3:49])(=[O:48])=[O:47])[C:27]([O:43][CH3:44])=[C:28]([NH:30][C:31]([C:33]2[S:37][C:36]3[C:38]([NH2:42])=[CH:39][CH:40]=[CH:41][C:35]=3[CH:34]=2)=[O:32])[CH:29]=1)([CH3:23])([CH3:22])[CH3:21].CNC>O=S(Cl)Cl.C1COCC1>[C:20]([C:24]1[CH:25]=[C:26]([NH:45][S:46]([CH3:49])(=[O:47])=[O:48])[C:27]([O:43][CH3:44])=[C:28]([NH:30][C:31]([C:33]2[S:37][C:36]3[C:38]([NH:42][C:7](=[O:9])[C:5]4[CH:4]=[C:3]([C:10](=[O:12])[N:15]([CH3:16])[CH3:13])[CH:2]=[N:1][CH:6]=4)=[CH:39][CH:40]=[CH:41][C:35]=3[CH:34]=2)=[O:32])[CH:29]=1)([CH3:23])([CH3:21])[CH3:22]

Participants

7

Reactant 4

HCID 674DimethylamineHCID 8471TriethylamineHCID 103663,5-Pyridinedicarboxylic acidHCID 103435957-Amino-benzo[b]thiophene-2-carboxylic acid (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl)-amide

Product 1

HCID 9986410N-[2-(5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenylcarbamoyl)-benzo[b]thiophen-7-yl]-5-(N,N-dimethylcarbamoyl)-nicotinamideYield 24%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 24386Thionyl ChlorideSolvent

Procedure

A suspension of pyridine-3,5-dicarboxylic acid (43.5 mg, 0.26 mmol) in 2.5 mL of SOCl2 was refluxed for 2.5 h to give a light yellow solution. The excess SOCl2 was removed by distillation and the resulting solid was dissolved in 2 mL of dry THF. Triethylamine (0.12 mL, 0.86 mmol) and a solution of 7-aminobenzo[b]thiophene-2-carboxylic acid (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl)-amide (39 mg, 0.087 mmol) in 2 mL of THF was added and the reaction mixture was stirred 12 h. A solution of dimethylamine (2.0 M in THF, 1 mL, 2 mmol) was added and the reaction mixture was stirred for additional 5 h. The reaction mixture was then extracted with EtOAc and purified by reverse phase HPLC on a C18 column eluting with an acetonitrile-water gradient to provide 12 mg (24%) of the title compound.

Workup

  1. temperaturewas refluxed for 2.5 h
  2. customto give a light yellow solution
  3. customThe excess SOCl2 was removed by distillation
  4. dissolutionthe resulting solid was dissolved in 2 mL of dry THF
  5. stirringthe reaction mixture was stirred for additional 5 h
  6. extractionThe reaction mixture was then extracted with EtOAc
  7. custompurified by reverse phase HPLC on a C18 column
  8. washeluting with an acetonitrile-water gradient

Sources & evidence

ORD record
ord-ab0dcebdf9f04b88ac7f3359e683c096
Source dataset
uspto-grants-2009_06
Patent number
US07550461B2

Reaction notes

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