Diisopropylethylamine → (4,4-Difluoro-azepan-1-yl)-(5-oxazol-4-yl-thiophen-3-yl)-methanone

HRID 2068665Notes

Reaction equation

HRID 2068665 reaction equation
FC(F)(F)C(O)=O.[F:8][C:9]1([F:16])[CH2:15][CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.[O:17]1[CH:21]=[C:20]([C:22]2[S:26][CH:25]=[C:24]([C:27](O)=[O:28])[CH:23]=2)[N:19]=[CH:18]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C1COCC1.C(Cl)Cl>[F:8][C:9]1([F:16])[CH2:15][CH2:14][CH2:13][N:12]([C:27]([C:24]2[CH:23]=[C:22]([C:20]3[N:19]=[CH:18][O:17][CH:21]=3)[S:26][CH:25]=2)=[O:28])[CH2:11][CH2:10]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 581102215-Oxazol-4-yl-thiophene-3-carboxylic acidHCID 668498474,4-Difluoro-azepane trifluoroacetate

Product 1

HCID 44226481(4,4-Difluoro-azepan-1-yl)-(5-oxazol-4-yl-thiophen-3-yl)-methanoneYield 30.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

4,4-Difluoro-azepane trifluoroacetate (Synthesis 47, 0.113 g, 0.45 mmol) was dissolved in THF (1 mL) and added to 5-oxazol-4-yl-thiophene-3-carboxylic acid (0.059 g, 0.30 mmol). DIPEA (0.154 mL, 0.90 mmol) was added followed by HATU (0.125 g, 0.33 mmol) and the reaction mixture was then stirred at room temperature overnight. The mixture was diluted with DCM then washed with aqueous sodium carbonate solution. The organics were dried over sodium sulfate, filtered and evaporated. The crude material was purified by HPLC, eluting with 5%-98% methanol in water (0.1% formic acid). The fractions containing the desired product were freeze-dried to give the title compound (0.029 g). LCMS m/z 313.15 [M+H]+ R.T.=8.31 min (Analytical Method 10).

Workup

  1. washthen washed with aqueous sodium carbonate solution
  2. dry with materialThe organics were dried over sodium sulfate
  3. filtrationfiltered
  4. customevaporated
  5. customThe crude material was purified by HPLC
  6. washeluting with 5%-98% methanol in water (0.1% formic acid)
  7. additionThe fractions containing the desired product
  8. customwere freeze-dried

Sources & evidence

ORD record
ord-4cd29bbaa9794b80909b070a6f4b5fe2
Source dataset
uspto-grants-2012_10
Patent number
US08299063B2

Reaction notes

Loading…