Triethylamine → (9-(2-Fluoro-5-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

HRID 446468Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 446468
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[CH:38]=[C:39]([CH2:44][CH2:45][OH:46])[CH:40]=[CH:41][C:42]=3[F:43])[CH2:32][CH2:31]2)[CH2:29][NH:28][CH2:27][CH2:26]1.[CH:47]([C:50]1[S:51][CH:52]=[C:53]([C:55](O)=[O:56])[N:54]=1)([CH3:49])[CH3:48].C(N(CC)CC)C>CN(C=O)C>[F:43][C:42]1[CH:41]=[CH:40][C:39]([CH2:44][CH2:45][OH:46])=[CH:38][C:37]=1[CH2:36][N:33]1[CH2:34][CH2:35][C:30]2([O:25][CH2:26][CH2:27][N:28]([C:55]([C:53]3[N:54]=[C:50]([CH:47]([CH3:49])[CH3:48])[S:51][CH:52]=3)=[O:56])[CH2:29]2)[CH2:31][CH2:32]1

Komponenten

6

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 225730652-(Propan-2-yl)-1,3-thiazole-4-carboxylic acidHCID 581684902-(3-(1-Oxa-4,9-diazaspiro[5.5]undecan-9-ylmethyl)-4-fluorophenyl)ethanol

Produkt 1

HCID 57989245(9-(2-Fluoro-5-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
20 °C

Versuchsvorschrift

HATU (1.1 g) was added in one portion to a cooled solution of 2-(3-(1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methyl)-4-fluorophenyl)ethanol [Example 44, step c] (0.7 g) and 2-isopropylthiazole-4-carboxylic acid (0.39 g) and triethylamine (0.95 mL) in DMF (15 mL). The reaction mixture was stirred at 20° C. for 1 hour and then partitioned between ethyl acetate and brine. The organic layer was washed with brine (×2), dried, filtered and the solvent removed under reduced pressure. The crude product was purified by flash silica chromatography, using 3% methanol in ethyl acetate containing 1% triethylamine as solvent. Fractions containing the product were evaporated to dryness to afford the subtitled compound. Yield 0.61 g.

Aufarbeitung

  1. custompartitioned between ethyl acetate and brine
  2. washThe organic layer was washed with brine (×2)
  3. customdried
  4. filtrationfiltered
  5. customthe solvent removed under reduced pressure
  6. customThe crude product was purified by flash silica chromatography
  7. additionFractions containing the product
  8. customwere evaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-055cffbcd3d940919d7118df8feae4fe
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08476265B2

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