Hydroxyamine hydrochloride → HCID 85428928, compound

HRID 571019Notes

Reaction equation

HRID 571019 reaction equation
C[O-].[Na+].C[O:5][C:6](=O)[CH:7]=[CH:8][C:9]1[CH:30]=[CH:29][C:12]2[N:13]([CH2:25][CH2:26][CH2:27][OH:28])[C:14]([CH2:16][CH:17]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH3:18])=[N:15][C:11]=2[CH:10]=1.Cl.[NH2:33][OH:34]>CO>[OH:34][NH:33][C:6](=[O:5])[CH:7]=[CH:8][C:9]1[CH:30]=[CH:29][C:12]2[N:13]([CH2:25][CH2:26][CH2:27][OH:28])[C:14]([CH2:16][CH:17]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH3:18])=[N:15][C:11]=2[CH:10]=1

Participants

5

Reactant 3

HCID 443297Hydroxyamine hydrochlorideHCID 10942334Sodium MethoxideHCID 68616042HCID 68616042, compound

Product 1

HCID 85428928HCID 85428928, compoundYield 6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Sodium methoxide (30% in methanol) (782 mg, 4.1 mmol) was added to a prestirred solution of 3-[1-(3-Hydroxy-propyl)-2-(2-phenyl-propyl)-1H-benzimidazol-5-yl]-acrylic acid methyl ester (130 mg, 0.34 mmol and hydroxylamine hydrochloride (242 mg, 3.4 mmol in MeOH (1.5 mL). The reaction mixture was continuously stirred for 40 minutes at room temperature and then poured into a solution of ice-water containing 1.0 mL concentrated hydrochloric acid. The mixture was extracted with dichloromethane. The organic layer was dried (MgSO4), filtered and concentrated. The desired product was separated by reverse phase preparative HPLC. After lyopholyzation, 7.8 mg (6%) of N-Hydroxy-3-[1-(3-hydroxy-propyl)-2-(2-phenyl-propyl)-1H-benzimidazol-5-yl]-acrylamide was obtained as powder. HPLC: 96%; tR=(LC/PDA: Phenomenex Luna C18 2.0×150 mm 5μ column; 0.8 mL/min, gradient 5-65% B over 15.5 min, Solvent A: H2O with 0.1% trifluoroacetic acid; Solvent B: Acetonitrile with 0.1% trifluoroacetic acid; UV 254): 7.22 min; 92%. 1H NMR (400 MHz, DMSO-d6) δ 1.35 (3H, d, J=6.5 Hz), 1.83 (2H, m), 3.00-4.00 (6H, m), 4.33 (2H, t, J=7.1 Hz), 6.55 (1H, d, J=15.8 Hz), 7.19-7.33 (5H, m), 7.62 (1H, d, J=15.8 Hz), 7.70 (1H, d, J=8.60 Hz), 7.82 (1H, d, J=8.60 Hz), 7.92 (1H, s), 10.15 (1H, bs), 10.33 (1H, bs). MS (m/z): 380 [MH]+.

Workup

  1. extractionThe mixture was extracted with dichloromethane
  2. dry with materialThe organic layer was dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe desired product was separated by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-a3d0846b21f14f919af3443ebd5273d2
Source dataset
uspto-grants-2015_05
Patent number
US09024029B2

Reaction notes

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