Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → (4,4-Difluoro-azepan-1-yl)-(5-phenyl-thiophen-3-yl)-methanone

HRID 2068661Notes

Reaction equation

HRID 2068661 reaction equation
[C:1]1([C:7]2[S:11][CH:10]=[C:9]([C:12]([OH:14])=O)[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[F:16][C:17]1([F:24])[CH2:23][CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(#N)C>[F:16][C:17]1([F:24])[CH2:23][CH2:22][CH2:21][N:20]([C:12]([C:9]2[CH:8]=[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[S:11][CH:10]=2)=[O:14])[CH2:19][CH2:18]1

Participants

5

Reactant 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 162272215-Phenylthiophene-3-carboxylic acidHCID 569243114,4-Difluoroazepane hydrochloride

Product 1

HCID 44226682(4,4-Difluoro-azepan-1-yl)-(5-phenyl-thiophen-3-yl)-methanoneYield 42%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

5-Phenyl-thiophene-3-carboxylic acid (0.20 g, 1.11 mmol) and 4,4-difluoro-azepane hydrochloride (0.19 g, 1.11 mmol) were stirred in acetonitrile (10 mL) with silica-supported diethylamine (1.32 mmol/g, 2.5 g) and HATU (0.40 g, 1.11 mmol) for 18 hours. The reaction mixture was filtered and the solvent was removed by evaporation then the crude material was purified by HPLC, eluting with 10%-98% acetonitrile in water (0.1% formic acid) over 20 minutes. The fractions containing the desired product were evaporated to give the title compound as a gum (0.15 g). LCMS m/z 322.19 [M+H]+ R.T.=11.14 min (Analytical Method 2).

Workup

  1. filtrationThe reaction mixture was filtered
  2. customthe solvent was removed by evaporation
  3. customthe crude material was purified by HPLC
  4. washeluting with 10%-98% acetonitrile in water (0.1% formic acid) over 20 minutes
  5. additionThe fractions containing the desired product
  6. customwere evaporated

Sources & evidence

ORD record
ord-f0c5e05aba7742eb82911aec9034ccb2
Source dataset
uspto-grants-2012_10
Patent number
US08299063B2

Reaction notes

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