Hydrochloric Acid → HCID 73231837, compound

HRID 1097853Notes

Reaction equation

HRID 1097853 reaction equation
CO[C:3](=[O:30])[CH:4]=[CH:5][C:6]1[CH:29]=[CH:28][C:9]2[N:10]([CH2:21][CH2:22][N:23]([CH2:26][CH3:27])[CH2:24][CH3:25])[C:11]([CH2:13][NH:14][C:15](=[O:20])[C:16]([CH3:19])([CH3:18])[CH3:17])=[N:12][C:8]=2[CH:7]=1.Cl.[NH2:32][OH:33].C[O-].[Na+].Cl>CO>[CH2:26]([N:23]([CH2:24][CH3:25])[CH2:22][CH2:21][N:10]1[C:9]2[CH:28]=[CH:29][C:6]([CH:5]=[CH:4][C:3]([NH:32][OH:33])=[O:30])=[CH:7][C:8]=2[N:12]=[C:11]1[CH2:13][NH:14][C:15](=[O:20])[C:16]([CH3:19])([CH3:17])[CH3:18])[CH3:27]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 443297Hydroxyamine hydrochlorideHCID 10942334Sodium MethoxideHCID 66812294HCID 66812294, compound

Product 1

HCID 73231837HCID 73231837, compoundYield 29.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of 3-{1-(2-diethylamino-ethyl)-2-[(2,2-dimethyl-propionylamino)-methyl]-1H-benzoimidazol-5-yl}-acrylic acid methyl ester (61-7, 73.8 mg, 0.18 mmol) and hydroxylamine hydrochloride (124 mg, 1.78 mmol) in MeOH (0.3 mL) was added sodium methoxide (30% in methanol) (0.8 mL, 3.6 mmol) at −78° C. The reaction mixture was then allowed to warm up slowly to room temperature. The reaction was monitored by LC/MS and was completed in around 15 min. 1N HCl was then added slowly into the reaction mixture at 0° C. The desired product was separated by reverse phase preparative HPLC. After lyopholyzation, 22.2 mg (24.3%) of 3-{1-(2-diethylamino-ethyl)-2-[(2,2-dimethyl-propionylamino)-methyl]-1H-benzoimidazol-5-yl}-N-hydroxy-acrylamide was obtained as powder. HPLC purity: 99.5%, tR=0.94 min. LCMS m/z: 416 ([M+H]+). 1H NMR (CD3OD) δ 7.89 (s, 1H), 7.84 (d, J=8.5 Hz, 1H), 7.73 (d, J=8.4 Hz, 1H), 7.55 (d, J=15.8 Hz, 1H), 6.53 (d, J=15.8 Hz, 1H), 4.98 (t, J=7.3 Hz, 2H), 4.73 (s, 2H), 3.75 (t, J=7.5 Hz, 2H), 3.42 (q, J=7.2 Hz, 4H), 1.37 (t, J=7.3 Hz, 6H), 1.22 (s, 9H); 13C NMR (CD3OD) δ 182.5, 168.9, 162.2, 161.9, 154.8, 140.8, 137.9, 135.0, 133.9, 126.0, 119.3, 117.1, 112.9, 50.9, 40.5, 39.7, 36.7, 27.6, 9.1.

Workup

  1. customThe desired product was separated by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-137ff4e929d147029a21b39b1417a895
Source dataset
uspto-grants-2012_03
Patent number
US08143282B2

Reaction notes

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