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 1253751ノート

反応式

HRID 1253751 の反応式
[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]

参加物

5

反応物 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

生成物 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)benzamide収率 72%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-998748693e264fb69fb85d4ee24ec854
出典データセット
uspto-grants-2013_06
特許番号
US08455475B2

反応ノート

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