Trifluoroacetic acid → 1-Oxa-4,9-diazaspiro[5,5]undecan-4-yl(2-(trifluoromethyl)thiazol-4-yl)methanone trifluoroacetate

HRID 471023ノート

反応式

HRID 471023 の反応式
Cl.[O:2]1[C:7]2([CH2:12][CH2:11][N:10](C(OC(C)(C)C)=O)[CH2:9][CH2:8]2)[CH2:6][NH:5][CH2:4][CH2:3]1.[F:20][C:21]([F:31])([F:30])[C:22]1[S:23][CH:24]=[C:25]([C:27](O)=[O:28])[N:26]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:56][C:57]([F:62])([F:61])[C:58]([OH:60])=[O:59]>CN(C=O)C.ClCCl.C1(C)C=CC=CC=1.C(N(CC)CC)C>[F:56][C:57]([F:62])([F:61])[C:58]([OH:60])=[O:59].[O:2]1[C:7]2([CH2:8][CH2:9][NH:10][CH2:11][CH2:12]2)[CH2:6][N:5]([C:27]([C:25]2[N:26]=[C:22]([C:21]([F:31])([F:20])[F:30])[S:23][CH:24]=2)=[O:28])[CH2:4][CH2:3]1

参加物

9

反応物 4

HCID 6422Trifluoroacetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 288755572-(Trifluoromethyl)-1,3-thiazole-4-carboxylic acidHCID 66964240Tert-butyl 1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate hydrochloride

生成物 1

HCID 866367511-Oxa-4,9-diazaspiro[5,5]undecan-4-yl(2-(trifluoromethyl)thiazol-4-yl)methanone trifluoroacetate

試薬・触媒・溶媒 4

HCID 1140Toluene溶媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒HCID 8471Triethylamine溶媒

反応条件

温度
0 °C

実験手順

A solution of tert-butyl 1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate hydrochloride (WuXi PharmaTech) (0.594 g) and 2-(trifluoromethyl)thiazole-4-carboxylic acid (0.4 g) in DMF (10 mL) was treated with triethylamine (0.848 mL) and cooled to 0° C. HATU (1.003 g) was added and the mixture stirred at 20° C. for 2 hours. 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. The crude product was purified by flash silica chromatography eluting with 40% ethyl acetate in isohexane to yield the product as the free base. This was dissolved in dichloromethane (40 mL) and treated with trifluoroacetic acid (10 mL) and then the mixture was allowed to stand at 20° C. for 1 hour. Toluene (60 mL) was added and the solvent removed under reduced pressure to afford the subtitled compound. Yield 0.740 g.

後処理

  1. customThe mixture was partitioned between ethyl acetate and brine
  2. washthe organic layer was washed twice with brine
  3. dry with materialdried over sodium sulphate
  4. filtrationfiltered
  5. customthe solvent evaporated under reduced pressure
  6. customThe crude product was purified by flash silica chromatography
  7. washeluting with 40% ethyl acetate in isohexane
  8. customto yield the product as the free base
  9. waitto stand at 20° C. for 1 hour
  10. customthe solvent removed under reduced pressure

出典と根拠

ORDレコード
ord-31ae822026264ea3a9333456986c7e23
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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