Dimethylamine → 2-[2-Hydroxy-5-(2-methoxy-pyridin-3-yl)-phenyl]-3H-benzoimidazole-5-carboxylic acid dimethylamide

HRID 470354Notes

Reaction equation

HRID 470354 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([O:14][CH3:15])=[N:10][CH:11]=[CH:12][CH:13]=2)=[CH:4][C:3]=1[C:16]1[NH:17][C:18]2[CH:24]=[C:23]([C:25]([OH:27])=O)[CH:22]=[CH:21][C:19]=2[N:20]=1.[CH3:28][NH:29][CH3:30].C1COCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:28][N:29]([CH3:30])[C:25]([C:23]1[CH:22]=[CH:21][C:19]2[N:20]=[C:16]([C:3]3[CH:4]=[C:5]([C:8]4[C:9]([O:14][CH3:15])=[N:10][CH:11]=[CH:12][CH:13]=4)[CH:6]=[CH:7][C:2]=3[OH:1])[NH:17][C:18]=2[CH:24]=1)=[O:27]

Participants

7

Reactant 5

HCID 674DimethylamineHCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 1361063252-[2-Hydroxy-5-(2-methoxy-pyridin-3-yl)-phenyl]-3H-benzoimidazole-5-carboxylic acid

Product 1

HCID 1361066482-[2-Hydroxy-5-(2-methoxy-pyridin-3-yl)-phenyl]-3H-benzoimidazole-5-carboxylic acid dimethylamideYield 80%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-[2-hydroxy-5-(2-methoxy-pyridin-3-yl)-phenyl]-3H-benzoimidazole-5-carboxylic acid (containing 1 equivalent of DMA, 44 mg, 0.1 mmol), dimethylamine in THF (0.5 mL, 2 M, 1 mmol) and HATU (38 mg, 0.1 mmol) in DMF (1.5 mL) was added DIEA (26 mg, 0.2 mmol). The reaction mixture was stirred at room temperature for 1 h and heated at 65° C. for 15 h, and then evaporated under reduced pressure. The residue was purified by chromatography (500:10:1 CH2Cl2/MeOH/28% aqueous NH4OH) to afford the title compound (31 mg, 80%). 1H NMR (MeOH-d4) δ 3.05 (s, 3H), 3.12 (s, 3H), 3.95 (s, 3H), 7.00-7.06 (2H), 7.31 (d, J=9 Hz, 1H), 7.52-7.75 (4H), 8.08-8.14 (2H). ESI-MS m/z 389.5 (MH+).

Workup

  1. temperatureheated at 65° C. for 15 h
  2. customevaporated under reduced pressure
  3. customThe residue was purified by chromatography (500:10:1 CH2Cl2/MeOH/28% aqueous NH4OH)

Sources & evidence

ORD record
ord-1a5180dbcf184bee9ca783e72816d643
Source dataset
uspto-grants-2014_01
Patent number
US08629147B2

Reaction notes

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