Acetic Acid → HCID 60207424, compound

HRID 1192204Notes

Reaction equation

HRID 1192204 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:25])[C:7]=1[S:8][C:9]1[S:13][C:12]([C:14]([NH:16][CH:17]2[CH2:21][CH2:20][NH:19][CH2:18]2)=[O:15])=[CH:11][C:10]=1[N+:22]([O-:24])=[O:23].[CH:26]1(OCCO[Si](C)(C)C)[CH2:28][CH2:27]1.C(O)(=O)C.[C-]#N.[BH4-].[Na+]>CO>[CH:26]1([N:19]2[CH2:20][CH2:21][CH:17]([NH:16][C:14]([C:12]3[S:13][C:9]([S:8][C:7]4[C:6]([Cl:25])=[CH:5][N:4]=[CH:3][C:2]=4[Cl:1])=[C:10]([N+:22]([O-:24])=[O:23])[CH:11]=3)=[O:15])[CH2:18]2)[CH2:28][CH2:27]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 57138593HCID 57138593, compoundHCID 60207421HCID 60207421, compoundHCID 131723130HCID 131723130, compound

Product 1

HCID 60207424HCID 60207424, compoundYield 5.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 5-((3,5-dichloropyridin-4-yl)thio)-4-nitro-N-(pyrrolidin-3-yl)thiophene-2-carboxamide (0.20 g, 0.48 mmol), (2-cyclopropoxyethoxy)trimethylsilane (498 mg, 2.86 mmol) and acetic acid (286 mg, 4.77 mmol) in methanol (10 mL) under nitrogen, was added sodium borohydride cyanide powder (150 mg, 2.38 mmol) by small portion. The resulting reaction mixture was heated under reflux for 4 hours. After this time, the reaction mixture was passed through a celite cartridge and the organic solution was concentrated. The resulting residue was dissolved in ethyl acetate and was washed with sodium bicarbonate solution and brine. The organic layer was separated, dried (Na2SO4) and concentrated. The crude was purified by reverse phase HPLC to afford the titled product as a solid (12.0 mg, 5% yield) 1H NMR (400 MHz, d6-DMSO) δ: 8.99 (2H, m), 8.87 (1H, d), 8.54 (1H, s), 4.23 (1H, m), 2.83 (2H, m), 2.07 (1H, m), 1.63 (2H, m), 1.23 (2H, m), 0.48 (2H, m), 0.38 (2H, m). MS m/z: 459.08, 461.07 [M+H]+.

Workup

  1. customThe resulting reaction mixture
  2. temperaturewas heated
  3. temperatureunder reflux for 4 hours
  4. concentrationthe organic solution was concentrated
  5. dissolutionThe resulting residue was dissolved in ethyl acetate
  6. washwas washed with sodium bicarbonate solution and brine
  7. customThe organic layer was separated
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. customThe crude was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-5afb45c4794443e9b599a5f0b115207c
Source dataset
uspto-grants-2014_03
Patent number
US08680139B2

Reaction notes

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