Formaldehyde → 2-(5-((2r)-1-Methylpyrrolidin-2-yl)thien-2-yl)-1h-benzimidazole-4-carboxamide

HRID 564223Notes

Reaction equation

HRID 564223 reaction equation
[NH:1]1[CH2:5][CH2:4][CH2:3][C@@H:2]1[C:6]1[S:10][C:9]([C:11]2[NH:15][C:14]3[CH:16]=[CH:17][CH:18]=[C:19]([C:20]([NH2:22])=[O:21])[C:13]=3[N:12]=2)=[CH:8][CH:7]=1.C=O.[C:25]([BH3-])#N.[Na+]>CO.O>[CH3:25][N:1]1[CH2:5][CH2:4][CH2:3][C@@H:2]1[C:6]1[S:10][C:9]([C:11]2[NH:15][C:14]3[CH:16]=[CH:17][CH:18]=[C:19]([C:20]([NH2:22])=[O:21])[C:13]=3[N:12]=2)=[CH:8][CH:7]=1

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 667602372-(5-((2r)-Pyrrolidin-2-yl)thien-2-yl)-1h-benzimidazole-4-carboxamide

Product 1

HCID 667588022-(5-((2r)-1-Methylpyrrolidin-2-yl)thien-2-yl)-1h-benzimidazole-4-carboxamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A solution of EXAMPLE 16D (50 mg) in methanol (20 mL) was treated with 37 wt % formaldehyde in water (114 μL) and stirred overnight. Sodium cyanoborohydride (315 mg) was added, and the solution was stirred for 3 hours and concentrated. The concentrate was dissolved in methanol and TFA, and purified by HPLC (Zorbax C-8, 0.1% TFA/acetonitrile/water). 1H NMR (CD3OD) δ 2.30 (m, 2H), 2.47 (m, 1H), 2.74 (m, 1H), 2.94 (s, 3H), 3.31-3.40 (m, 1H), 3.88 (m, 1H), 4.81 (m, 1H), 7.40 (t, J=7.7 Hz, 1H), 7.51 (d, J=3.7 Hz, 1H), 7.73 (d, J=7.6 Hz, 1H), 7.86 (d, J=4.0 Hz, 1H), 7.95 (d, J=7.6 Hz, 1H).

Workup

  1. stirringthe solution was stirred for 3 hours
  2. concentrationconcentrated
  3. dissolutionThe concentrate was dissolved in methanol
  4. customTFA, and purified by HPLC (Zorbax C-8, 0.1% TFA/acetonitrile/water)

Sources & evidence

ORD record
ord-361845f7a3cd442ea76248c3db346514
Source dataset
uspto-grants-2011_11
Patent number
US08067613B2

Reaction notes

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