Triethylamine → (9-(3-Fluoro-5-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-propylthiazol-4-yl)methanone

HRID 471113Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 471113
F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[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]=[C:41]([F:43])[CH:42]=3)[CH2:32][CH2:31]2)[CH2:29][NH:28][CH2:27][CH2:26]1.[CH2:47]([C:50]1[S:51][CH:52]=[C:53]([C:55](O)=[O:56])[N:54]=1)[CH2:48][CH3:49].C(N(CC)CC)C>CN(C=O)C>[F:43][C:41]1[CH:42]=[C:37]([CH:38]=[C:39]([CH2:44][CH2:45][OH:46])[CH:40]=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]([CH2:47][CH2:48][CH3:49])[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 184357622-Propyl-1,3-thiazole-4-carboxylic acidHCID 579889902-(3-(1-Oxa-4,9-diazaspiro[5.5]undecan-9-ylmethyl)-5-fluorophenyl)ethanol

Produkt 1

HCID 57989199(9-(3-Fluoro-5-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-propylthiazol-4-yl)methanone

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.25 g) was added to a solution of 2-(3-(1-oxa-4,9-diazaspiro[5.5]undecan-9-ylmethyl)-5-fluorophenyl)ethanol (example 55, step c) (0.16 g), 2-propylthiazole-4-carboxylic acid (example 56, step c) (0.09 g) and triethylamine (0.29 mL) in DMF (7 mL) and the resulting yellow solution was stirred for 30 min. The mixture was partitioned between ethyl acetate (100 mL) and brine (100 mL). The organic phase was separated, washed with brine (2×100 mL), dried over sodium sulphate, filtered and the solvent evaporated. The resulting gum was purified by silica gel chromatography eluting with 47.5:47.5:5 isohexane:ethyl acetate:triethylamine to 95:5 ethyl acetate:triethylamine gradient. The fractions containing product were combined, toluene (200 mL) was added, and the mixture evaporated to give the subtitled compound as a clear gum. Yield 0.14 g.

Aufarbeitung

  1. customThe mixture was partitioned between ethyl acetate (100 mL) and brine (100 mL)
  2. customThe organic phase was separated
  3. washwashed with brine (2×100 mL)
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. customthe solvent evaporated
  7. customThe resulting gum was purified by silica gel chromatography
  8. washeluting with 47.5:47.5:5 isohexane
  9. additionThe fractions containing product
  10. additiontoluene (200 mL) was added
  11. customthe mixture evaporated

Quellen und Nachweise

ORD-Eintrag
ord-c2bd04c43fec44a991f7a94834805a38
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08629271B2

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