Diisopropylethylamine → HCID 72948197, compound

HRID 1775459Notes

Reaction equation

HRID 1775459 reaction equation
[F:1][CH:2]([F:23])[C:3]([NH:5][CH2:6][CH2:7][C:8]1[C:16]2[C:11](=[CH:12][C:13]([F:19])=[C:14]([O:17][CH3:18])[CH:15]=2)[NH:10][C:9]=1[C:20]([OH:22])=O)=[O:4].Cl.CN.[CH:27]([N:30](C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CN(C)C=O>[F:23][CH:2]([F:1])[C:3]([NH:5][CH2:6][CH2:7][C:8]1[C:16]2[C:11](=[CH:12][C:13]([F:19])=[C:14]([O:17][CH3:18])[CH:15]=2)[NH:10][C:9]=1[C:20]([NH:30][CH3:27])=[O:22])=[O:4]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 6364545Methylamine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 118071577HCID 118071577, compound

Product 1

HCID 72948197HCID 72948197, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 3-{2-[(difluoroacetyl)amino]ethyl}-6-fluoro-5-methoxy-1H-indole-2-carboxylic acid (2.48 g), methylamine hydrochloride (2.54 g), diisopropylethylamine (9.00 mL), and N,N-dimethyl formamide (49.6 mL) was added 2-(7-aza-1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (8.57 g), followed by stirring at room temperature for 1 hour. To the mixture was added ice water, followed by extraction with ethyl acetate and further extraction with chloroform/methanol (10:1). The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The insoluble materials were separated by filtration, the filtrate was concentrated under reduced pressure, and then the obtained residue was purified by silica gel column chromatography (chloroform:methanol=100:0 to 10:1) to obtain 3-{2-[(difluoroacetyl)amino]ethyl}-6-fluoro-5-methoxy-N-methyl-1H-indole-2-carboxamide (1.42 g).

Workup

  1. extractionfollowed by extraction with ethyl acetate and further extraction with chloroform/methanol (10:1)
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe insoluble materials were separated by filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customthe obtained residue was purified by silica gel column chromatography (chloroform:methanol=100:0 to 10:1)

Sources & evidence

ORD record
ord-9bffddfdcfd04ce296f8eb9c2d0d7426
Source dataset
uspto-grants-2016_02
Patent number
US09260445B2

Reaction notes

Loading…