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

HRID 471121노트

반응식

HRID 471121 반응식
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.[CH:47]1([C:51]2[S:52][CH:53]=[C:54]([C:56](O)=[O:57])[N:55]=2)[CH2:50][CH2:49][CH2:48]1.C(N(CC)CC)C>CN(C=O)C>[CH:47]1([C:51]2[S:52][CH:53]=[C:54]([C:56]([N:28]3[CH2:29][C:30]4([CH2:35][CH2:34][N:33]([CH2:36][C:37]5[CH:38]=[C:39]([CH2:44][CH2:45][OH:46])[CH:40]=[C:41]([F:43])[CH:42]=5)[CH2:32][CH2:31]4)[O:25][CH2:26][CH2:27]3)=[O:57])[N:55]=2)[CH2:48][CH2:49][CH2:50]1

참가 물질

6

반응물 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 200843232-Cyclobutylthiazole-4-carboxylic acidHCID 579889902-(3-(1-Oxa-4,9-diazaspiro[5.5]undecan-9-ylmethyl)-5-fluorophenyl)ethanol

생성물 1

HCID 57989217(2-Cyclobutylthiazol-4-yl)(9-(3-fluoro-5-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.32 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) (0.2 g), 2-cyclobutylthiazole-4-carboxylic acid (example 58, step c) (0.12 g) and triethylamine (0.36 mL) in DMF (7 mL) and the resulting yellow solution was stirred for 30 min. The mixture was partitioned between ethyl acetate and brine (100 mL) and the layers separated. The organic phase was 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 solvent evaporated to give the subtitled compound as a clear oil. Yield 0.18 g.

후처리

  1. customThe mixture was partitioned between ethyl acetate and brine (100 mL)
  2. customthe layers separated
  3. washThe organic phase was washed 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 solvent evaporated

출처 및 근거

ORD 기록
ord-2dfd082b3140430abf2f498d1f161dc9
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08629271B2

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