Ammonia → (2-tert-Butylthiazol-4-yl)(9-(3-fluoro-5-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone

HRID 1689326Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1689326
[F:1][C:2]1[CH:3]=[C:4]([CH:30]=[C:31]([CH2:33][CH2:34][OH:35])[CH:32]=1)[CH2:5][N:6]1[CH2:29][CH2:28][C:9]2([O:14][CH2:13][CH2:12][N:11]([C:15]([C:17]3[N:18]=[C:19]([C:22]4[CH:27]=CC=C[CH:23]=4)[S:20][CH:21]=3)=[O:16])[CH2:10]2)[CH2:8][CH2:7]1.N.[CH3:37]O>>[C:22]([C:19]1[S:20][CH:21]=[C:17]([C:15]([N:11]2[CH2:10][C:9]3([CH2:28][CH2:29][N:6]([CH2:5][C:4]4[CH:30]=[C:31]([CH2:33][CH2:34][OH:35])[CH:32]=[C:2]([F:1])[CH:3]=4)[CH2:7][CH2:8]3)[O:14][CH2:13][CH2:12]2)=[O:16])[N:18]=1)([CH3:37])([CH3:23])[CH3:27]

Komponenten

4

Edukt 3

HCID 222AmmoniaHCID 887MethanolHCID 57989277(9-(3-Fluoro-5-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-phenylthiazol-4-yl)methanone

Produkt 1

HCID 57989343(2-tert-Butylthiazol-4-yl)(9-(3-fluoro-5-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone

Reaktionsbedingungen

Temperatur
20 °C

Versuchsvorschrift

A solution of 2,2,2-trifluoro-1-(9-(3-fluoro-5-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)ethanone (example 41, step d) (0.21 g) in methanol (3 mL) was added to ammonia (35% aqueous solution, 15 mL) and the reaction mixture stirred at 20° C. for 1 hour. The mixture was evaporated to dryness under reduced pressure and the residue azeotroped three times with acetonitrile. The residue was dissolved in DMF (7 mL) and treated with 2-tert-butylthiazole-4-carboxylic acid (0.096 g) followed by triethylamine (0.290 mL) and then HATU (0.257 g) and the resultant mixture stirred at 20° C. for 1 hour. The mixture was partitioned between ethyl acetate and brine, the organic layer was washed twice with brine, dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure to afford the subtitled compound. Yield 0.22 g.

Aufarbeitung

  1. customThe mixture was evaporated to dryness under reduced pressure
  2. customthe residue azeotroped three times with acetonitrile
  3. dissolutionThe residue was dissolved in DMF (7 mL)
  4. additiontreated with 2-tert-butylthiazole-4-carboxylic acid (0.096 g)
  5. stirringHATU (0.257 g) and the resultant mixture stirred at 20° C. for 1 hour
  6. customThe mixture was partitioned between ethyl acetate and brine
  7. washthe organic layer was washed twice with brine
  8. dry with materialdried over sodium sulphate
  9. filtrationfiltered
  10. customthe solvent evaporated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-38f2753d634647178dcce91da7e2b148
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08148373B2

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