Triethylamine → (9-(2-Fluoro-3-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-(pentan-3-yl)thiazol-4-yl)methanone

HRID 446435

Reaktionsgleichung

Reaktionsgleichung von HRID 446435
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[O:25]1[C:30]2([CH2:35][CH2:34][N:33]([CH2:36][C:37]3[C:38]([F:46])=[C:39]([CH2:43][CH2:44][OH:45])[CH:40]=[CH:41][CH:42]=3)[CH2:32][CH2:31]2)[CH2:29][NH:28][CH2:27][CH2:26]1.[CH3:47][CH2:48][CH:49]([C:52]1[S:53][CH:54]=[C:55]([C:57](O)=[O:58])[N:56]=1)[CH2:50][CH3:51].C(N(CC)CC)C>CN(C=O)C.[Cl-].[Na+].O.O>[F:46][C:38]1[C:39]([CH2:43][CH2:44][OH:45])=[CH:40][CH:41]=[CH:42][C:37]=1[CH2:36][N:33]1[CH2:34][CH2:35][C:30]2([O:25][CH2:26][CH2:27][N:28]([C:57]([C:55]3[N:56]=[C:52]([CH:49]([CH2:50][CH3:51])[CH2:48][CH3:47])[S:53][CH:54]=3)=[O:58])[CH2:29]2)[CH2:31][CH2:32]1

Komponenten

8

Edukt 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 579605932-(Pentan-3-yl)thiazole-4-carboxylic acidHCID 579891872-(3-(1-Oxa-4,9-diazaspiro[5.5]undecan-9-ylmethyl)-2-fluorophenyl)ethanol

Produkt 1

HCID 57989379(9-(2-Fluoro-3-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-(pentan-3-yl)thiazol-4-yl)methanone

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 57417360Sodium chloride; waterLösungsmittel

Versuchsvorschrift

HATU (0.35 g) was added to a colourless solution of 2-(3-(1-oxa-4,9-diazaspiro[5.5]undecan-9-ylmethyl)-2-fluorophenyl)ethanol [Example 9, step b] (0.364 g), 2-(pentan-3-yl)thiazole-4-carboxylic acid [Carboxylic Acid 3] (0.141 g) and triethylamine (0.30 mL) in DMF (10 mL), pre-cooled in ice-water. The resulting yellow mixture was stirred in ice-water for 1 hour, then at room temperature for 1 hour. The solution was poured into a mixture of water and brine and extracted twice with ethyl acetate. The combined organic extracts were washed three times with water, once with brine, then dried (MgSO4), filtered and concentrated onto flash silica in vacuo. The resulting powder was purified by flash chromatography on silica eluted with triethylamine:methanol:dichloromethane (1:2:97) to afford the subtitled compound. Yield 0.324 g.

Aufarbeitung

  1. extractionextracted twice with ethyl acetate
  2. washThe combined organic extracts were washed three times with water
  3. dry with materialonce with brine, then dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated onto flash silica in vacuo
  6. customThe resulting powder was purified by flash chromatography on silica
  7. washeluted with triethylamine:methanol:dichloromethane (1:2:97)

Quellen und Nachweise

ORD-Eintrag
ord-57ccb75b7ead4277af33de70c1cc1cf7
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08476265B2

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