Diisopropylethylamine → (3R)-N-Methyl-N-(1-pyridin-4-yl-piperidin-4-yl)-3-(3,3,3-trifluoropropanoyl-amino)-2,3-dihydro-1H-indene-5-carboxylic acid amide

HRID 1193420Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1193420
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[F:34][C:35]([F:41])([F:40])[CH2:36][C:37](O)=[O:38].[NH2:42][C@H:43]1[C:51]2[C:46](=[CH:47][CH:48]=[C:49]([C:52]([N:54]([CH3:67])[CH:55]3[CH2:60][CH2:59][N:58]([C:61]4[CH:66]=[CH:65][N:64]=[CH:63][CH:62]=4)[CH2:57][CH2:56]3)=[O:53])[CH:50]=2)[CH2:45][CH2:44]1>C1COCC1.ClCCl>[CH3:67][N:54]([CH:55]1[CH2:60][CH2:59][N:58]([C:61]2[CH:66]=[CH:65][N:64]=[CH:63][CH:62]=2)[CH2:57][CH2:56]1)[C:52]([C:49]1[CH:50]=[C:51]2[C:46](=[CH:47][CH:48]=1)[CH2:45][CH2:44][C@H:43]2[NH:42][C:37](=[O:38])[CH2:36][C:35]([F:41])([F:40])[F:34])=[O:53]

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 27779723,3,3-Trifluoropropionic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66798813(R)-3-Amino-N-methyl-N-(1-(pyridin-4-yl)piperidin-4-yl)-2,3-dihydro-1H-indene-5-carboxamide

Produkt 1

HCID 56941868(3R)-N-Methyl-N-(1-pyridin-4-yl-piperidin-4-yl)-3-(3,3,3-trifluoropropanoyl-amino)-2,3-dihydro-1H-indene-5-carboxylic acid amideAusbeute 59 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

HATU (168 mg, 0.44 mmol, 1 eq) and DIPEA (200 μl, 1.1 mmol, 2.5 eq) were added to an ice-cooled solution of 3,3,3-trifluoropropionic acid (67.5 mg, 0.528 mmol, 1.2 eq) in THF (5 ml), and the mixture was stirred for 30 min. (R)-3-Amino-N-methyl-N-(1-(pyridin-4-yl)piperidin-4-yl)-2,3-dihydro-1H-indene-5-carboxamide (154 mg, 0.44 mmol, 1 eq) was dissolved in THF (2 ml) and added dropwise to the reaction solution, and stirring was carried out for 16 h at RT. The reaction solution was diluted with dichloromethane (100 ml), washed with sat. sodium hydrogen carbonate solution (40 ml), sat. ammonium chloride solution (40 ml), water (40 ml) and sat. NaCl solution (40 ml), dried over sodium sulfate and concentrated under reduced pressure. After purification by column chromatography (silica gel, 5% MeOH in dichloromethane), the desired product was obtained in the form of a white solid. Yield: 59% (120 mg, 0.26 mmol).

Aufarbeitung

  1. additionadded dropwise to the reaction solution
  2. washwashed with sat. sodium hydrogen carbonate solution (40 ml), sat. ammonium chloride solution (40 ml), water (40 ml) and sat. NaCl solution (40 ml)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customAfter purification by column chromatography (silica gel, 5% MeOH in dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-21a41d485c0242dba20bff4ab0593b3a
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08680159B2

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