Diisopropylethylamine → 2-{[6-(3-Methanesulfonyl-phenylethynyl)-pyridine-2-carbonyl]-amino}-1H-benzoimidazole-4-carboxylic acid methyl ester

HRID 1910196

Reaction equation

HRID 1910196 reaction equation
[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]#[C:12][C:13]2[N:18]=[C:17]([C:19]([OH:21])=O)[CH:16]=[CH:15][CH:14]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH3:55][O:56][C:57]([C:59]1[C:67]2[N:66]=[C:65]([NH2:68])[NH:64][C:63]=2[CH:62]=[CH:61][CH:60]=1)=[O:58]>CN(C=O)C>[CH3:55][O:56][C:57]([C:59]1[C:67]2[N:66]=[C:65]([NH:68][C:19]([C:17]3[CH:16]=[CH:15][CH:14]=[C:13]([C:12]#[C:11][C:7]4[CH:8]=[CH:9][CH:10]=[C:5]([S:2]([CH3:1])(=[O:3])=[O:4])[CH:6]=4)[N:18]=3)=[O:21])[NH:64][C:63]=2[CH:62]=[CH:61][CH:60]=1)=[O:58]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 24730367methyl 2-amino-1H-benzo[d]imidazole-4-carboxylate2×HCID 669406666-(3-Methanesulfonyl-phenylethynyl)-pyridine-2-carboxylic acid

Product 1

HCID 669402052-{[6-(3-Methanesulfonyl-phenylethynyl)-pyridine-2-carbonyl]-amino}-1H-benzoimidazole-4-carboxylic acid methyl esterYield 66.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 136 mg (0.45 mmol) of 6-(3-methanesulfonyl-phenylethynyl)-pyridine-2-carboxylic acid in DMF (2 mL) was added 210 mg (0.55 mmol) of HBTU (210 mg) and DIEA (0.2 mL). The mixture was stirred for 5 min then 96 mg (0.5 mmol) of 2-amino-1H-benzoimidazole-4-carboxylic acid methyl ester (Intermediate A) was added. The reaction mixture was stirred at 30° C. for 30 min. After usual workup as described in general procedure A, 142 mg (60%) of 2-{[6-(3-Methanesulfonyl-phenylethynyl)-pyridine-2-carbonyl]-amino}-1H-benzoimidazole-4-carboxylic acid methyl ester was obtained after column chromatography eluting with DCM/EtOAc (v/v=1:1) then EtOAc. LCMS: 475 (M+1)+. This ester was hydrolyzed as described in general procedure B to provide 135 mg (100%) of 2-{[6-(3-methanesulfonyl-phenylethynyl)-pyridine-2-carbonyl]-amino}-1H-benzoimidazole-4-carboxylic acid. LCMS: 461 (M+1)+.

Workup

  1. stirringThe reaction mixture was stirred at 30° C. for 30 min

Sources & evidence

ORD record
ord-e3000823aa144ff78b7a9a3d1e16865b
Source dataset
uspto-grants-2013_12
Patent number
US08598353B2

Linked notes

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