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

HRID 1689355노트

반응식

HRID 1689355 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:52]2[S:53][CH:54]=[C:55]([C:57](O)=[O:58])[N:56]=2)[CH2:51][CH2:50][CH2:49][CH2:48]1.C(N(CC)CC)C>CN(C=O)C>[CH:47]1([C:52]2[S:53][CH:54]=[C:55]([C:57]([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:58])[N:56]=2)[CH2:48][CH2:49][CH2:50][CH2:51]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 579889902-(3-(1-Oxa-4,9-diazaspiro[5.5]undecan-9-ylmethyl)-5-fluorophenyl)ethanolHCID 579891322-Cyclopentylthiazole-4-carboxylic acid

생성물 1

HCID 57989165(2-Cyclopentylthiazol-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 (0.33 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) (0.21 g), 2-cyclopentylthiazole-4-carboxylic acid (example 59, step d) (0.13 g) and triethylamine (0.38 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), 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 under reduced pressure to give the subtitled compound as a clear gum. Yield 0.19 g.

후처리

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

출처 및 근거

ORD 기록
ord-b405e67321fb4f93976481994c2d482d
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08148373B2

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