Formic Acid → (R)-N,N-dimethyl-2-(5-(1-methylpyrrolidin-3-ylsulfonyl)-2-neopentyl-1H-benzo[d]imidazol-1-yl)ethanamine

HRID 241675Notes

Reaction equation

HRID 241675 reaction equation
[CH3:1][N:2]([CH3:27])[CH2:3][CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][C:12]([S:14]([C@@H:17]3[CH2:21][CH2:20][NH:19][CH2:18]3)(=[O:16])=[O:15])=[CH:13][C:8]=2[N:7]=[C:6]1[CH2:22][C:23]([CH3:26])([CH3:25])[CH3:24].C=O.[CH:30](O)=O>O1CCOCC1>[CH3:1][N:2]([CH3:27])[CH2:3][CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][C:12]([S:14]([C@@H:17]3[CH2:21][CH2:20][N:19]([CH3:30])[CH2:18]3)(=[O:15])=[O:16])=[CH:13][C:8]=2[N:7]=[C:6]1[CH2:22][C:23]([CH3:24])([CH3:26])[CH3:25]

Participants

5

Reactant 3

HCID 284Formic AcidHCID 712FormaldehydeHCID 58513585(R)-N,N-dimethyl-2-(2-neopentyl-5-(pyrrolidin-3-ylsulfonyl)-1H-benzo[d]imidazol-1-yl)ethanamine

Product 1

HCID 46851890(R)-N,N-dimethyl-2-(5-(1-methylpyrrolidin-3-ylsulfonyl)-2-neopentyl-1H-benzo[d]imidazol-1-yl)ethanamineYield 89.6%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of (R)—N,N-dimethyl-2-(2-neopentyl-5-(pyrrolidin-3-ylsulfonyl)-1H-benzo[d]imidazol-1-yl)ethanamine (STEP C, 453 mg, 1.15 mmol) in 1,4-dioxane (5 mL) was added 37% formalin (343 microL, 4.27 mmol) and formic acid (221 microL, 5.77 mmol) at 0° C. The mixture was stirred at 45° C. for 1 h. The mixture was concentrated in vacuo. The residue was diluted with sodium bicarbonate aqueous solution and extracted with ethyl acetate (60 mL×2). The combined organic layers were washed with brine and dried over sodium sulfate. The resulting solution was concentrated and residue was purified by amine gel column chromatography (dichloromethane-ethyl acetate, gradient) to give the title compound (419 mg, 89%) as a clear grease.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. additionThe residue was diluted with sodium bicarbonate aqueous solution
  3. extractionextracted with ethyl acetate (60 mL×2)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationThe resulting solution was concentrated
  7. customresidue was purified by amine gel column chromatography (dichloromethane-ethyl acetate, gradient)

Sources & evidence

ORD record
ord-e1815d40218444c8a381e93c2f516b12
Source dataset
uspto-grants-2014_02
Patent number
US08653063B2

Reaction notes

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