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 1253751노트

반응식

HRID 1253751 반응식
[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]

참가 물질

5

반응물 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

생성물 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)benzamide수율 72%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-998748693e264fb69fb85d4ee24ec854
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08455475B2

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