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 471096ノート

反応式

HRID 471096 の反応式
[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]

参加物

4

反応物 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

生成物 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

反応条件

温度
20 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-7fba2e88c9744c3abaa97ffed0fa64f4
出典データセット
uspto-grants-2014_01
特許番号
US08629271B2

反応ノート

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