Triethylamine → N-({6-[(2-Fluoroethyl)amino]-4-(methylthio)pyridin-2-yl}carbamoyl)-5-(2-methoxyethyl)-4-methylthiophene-2-sulfonamide

HRID 1696746Notes

Reaction equation

HRID 1696746 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][C:5]1[S:9][C:8]([S:10]([NH2:13])(=[O:12])=[O:11])=[CH:7][C:6]=1[CH3:14].Cl[C:16](OC1C=CC=CC=1)=[O:17].C(N(CC)CC)C.[F:32][CH2:33][CH2:34][NH:35][C:36]1[CH:41]=[C:40]([S:42][CH3:43])[CH:39]=[C:38]([NH2:44])[N:37]=1>C(#N)C>[F:32][CH2:33][CH2:34][NH:35][C:36]1[N:37]=[C:38]([NH:44][C:16]([NH:13][S:10]([C:8]2[S:9][C:5]([CH2:4][CH2:3][O:2][CH3:1])=[C:6]([CH3:14])[CH:7]=2)(=[O:12])=[O:11])=[O:17])[CH:39]=[C:40]([S:42][CH3:43])[CH:41]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 67274431HCID 67274431, compoundHCID 86630931HCID 86630931, compound

Product 1

HCID 42629873N-({6-[(2-Fluoroethyl)amino]-4-(methylthio)pyridin-2-yl}carbamoyl)-5-(2-methoxyethyl)-4-methylthiophene-2-sulfonamideYield 23.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
60 °C

Procedure

5-(2-Methoxy-ethyl)-4-methyl-thiophene-2-sulfonic acid amide (0.063 g, 0.373 mmol) was dissolved in 2.2 mL of abs. acetonitrile and treated successively with phenyl chloroformate (0.058 g, 1.0 eq.) and triethylamine (0.129 mL, 2.5 eq.), and the mixture kept at ambient temperature for 1 h. The below prepared N-(2-fluoro-ethyl)-4-methylsulfanyl-pyridine-2,6-diamine (0.094 g, 1.0 eq.), dissolved in a tiny amount of acetonitrile, was then added, and the mixture heated to 60° C. for 18 h. Cooling, pouring onto crashed ice, twofold extraction with AcOEt, washing with water and brine, drying over sodium sulfate, and evaporation of the solvents, followed by flash chromatography (SiO2, hexane/AcOEt=4/6) and crystallization from AcOEt, yielded eventually 0.041 g of the title compound as off-white crystals.

Workup

  1. additionwas then added
  2. temperatureCooling
  3. additionpouring
  4. extractionice, twofold extraction with AcOEt
  5. washwashing with water and brine
  6. dry with materialdrying over sodium sulfate, and evaporation of the solvents
  7. customfollowed by flash chromatography (SiO2, hexane/AcOEt=4/6) and crystallization from AcOEt

Sources & evidence

ORD record
ord-0d1e6cb8e1dc46ea8aeb836f3cd6a1d8
Source dataset
uspto-grants-2012_04
Patent number
US08163778B2

Reaction notes

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