Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → 2-Chloro-N-(6-(8-(2,2,2-trifluoroacetyl)-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl)benzamide

HRID 1253751Notes

Reaction equation

HRID 1253751 reaction equation
[Cl:1][C:2]1[CH:22]=[CH:21][CH:20]=[CH:19][C:3]=1[C:4]([NH:6][CH:7]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:16]([OH:18])=O)[CH:14]=2)[CH2:9][CH2:8]1)=[O:5].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:47][C:48]([F:62])([F:61])[C:49]([N:51]1[CH2:60][CH2:59][C:54]2([CH2:58][NH:57][CH2:56][CH2:55]2)[CH2:53][CH2:52]1)=[O:50]>C1COCC1>[Cl:1][C:2]1[CH:22]=[CH:21][CH:20]=[CH:19][C:3]=1[C:4]([NH:6][CH:7]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:16]([N:57]3[CH2:56][CH2:55][C:54]4([CH2:53][CH2:52][N:51]([C:49](=[O:50])[C:48]([F:61])([F:62])[F:47])[CH2:60][CH2:59]4)[CH2:58]3)=[O:18])[CH:14]=2)[CH2:9][CH2:8]1)=[O:5]

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 595052323-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carboxylic acidHCID 595052392,2,2-Trifluoro-1-(2,8-diazaspiro[4.5]decan-8-yl)ethanone

Product 1

HCID 595057192-Chloro-N-(6-(8-(2,2,2-trifluoroacetyl)-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl)benzamideYield 72%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of 3-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carboxylic acid (E-01) (789 mg, 2.49 mmol, 1.0 eq.) in THF (20 ml) was added HATU (1.04 g, 2.76 mmol, 1.1 equiv.) and DI PEA (2.1 ml, 12.4 mmol, 5 eq.) at 0° C. and the reaction mixture was allowed to stir for 15 min. A solution of 2,2,2-trifluoro-1-(2,8-diazaspiro[4.5]decan-8-yl)ethanone (587 mg, 2.49 mmol, 1.0 equiv.) in THF (5 ml) was then added and the reaction mixture was stirred at 25° C. for 15 h. The mixture was diluted with MC (300 ml) and washed successively with sodium bicarbonate solution (40 ml), ammonium chloride solution (50 ml), water (50 ml) and brine (50 ml). The organic layer was dried over sodium sulfate and the solvent evaporated under reduced pressure to obtain the crude material which was purified by column chromatography (silica gel; 0-3% methanol/MC) to yield the pure final product as a white solid. Yield: 72% (1 g, 1.8 mmol).

Workup

  1. stirringthe reaction mixture was stirred at 25° C. for 15 h
  2. additionThe mixture was diluted with MC (300 ml)
  3. washwashed successively with sodium bicarbonate solution (40 ml), ammonium chloride solution (50 ml), water (50 ml) and brine (50 ml)
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. customthe solvent evaporated under reduced pressure
  6. customto obtain the crude material which
  7. customwas purified by column chromatography (silica gel; 0-3% methanol/MC)

Sources & evidence

ORD record
ord-998748693e264fb69fb85d4ee24ec854
Source dataset
uspto-grants-2013_06
Patent number
US08455475B2

Reaction notes

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