Piperidine → (2-Bromo-5-phenyl-thiophen-3-yl)-piperidin-1-yl-methanone

HRID 2068604ノート

反応式

HRID 2068604 の反応式
[Br:1][C:2]1[S:3][C:4]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:5][C:6]=1[C:7]([OH:9])=O.CCN(C(C)C)C(C)C.CN(C(ON1N=N[C:35]2[CH:36]=[CH:37][CH:38]=[N:39][C:34]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.N1CCCCC1>CN(C=O)C>[Br:1][C:2]1[S:3][C:4]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:5][C:6]=1[C:7]([N:39]1[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38]1)=[O:9]

参加物

6

反応物 4

HCID 8082PiperidineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 581103102-Bromo-5-phenylthiophene-3-carboxylic acid

生成物 1

HCID 44225122(2-Bromo-5-phenyl-thiophen-3-yl)-piperidin-1-yl-methanone収率 7.7%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

2-Bromo-5-phenyl-thiophene-3-carboxylic acid (0.99 g, 3.5 mmol) was dissolved in DMF (20 mL). DIPEA (7.0 mmol), HATU (3.5 mmol) and piperidine (3.5 mmol) were added and the solution stirred at room temperature. The reaction mixture was partitioned between ethyl acetate and 1 N hydrochloric acid. The organic solution was dried over magnesium sulfate, filtered and the solvent evaporated. The residue was purified by flash chromatography on silica, eluting with 0%-50% ethyl acetate in cyclohexane. The fractions containing the desired product were concentrated under vacuum to give a solid which was further purified by HPLC, eluting with 50%-90% acetonitrile in water (0.1% formic acid) over 30 minutes. The fractions containing the desired product were concentrated under vacuum then freeze-dried to give the title compound (95 mg). LCMS m/z 350.07 [M+H]+ R.T.=12.57 min (Analytical Method 1). 1H NMR (400 MHz, CHCl3-d): δ 7.50 (d, 1H), 7.40 (t, 2H), 7.3 (m, 1H), 7.1 (s, 1H), 3.7 (m, 2H), 3.4 (t, 2H), 1.7 (m, 4H), 1.6 (m, 2H).

後処理

  1. customThe reaction mixture was partitioned between ethyl acetate and 1 N hydrochloric acid
  2. dry with materialThe organic solution was dried over magnesium sulfate
  3. filtrationfiltered
  4. customthe solvent evaporated
  5. customThe residue was purified by flash chromatography on silica
  6. washeluting with 0%-50% ethyl acetate in cyclohexane
  7. additionThe fractions containing the desired product
  8. concentrationwere concentrated under vacuum
  9. customto give a solid which
  10. customwas further purified by HPLC
  11. washeluting with 50%-90% acetonitrile in water (0.1% formic acid) over 30 minutes
  12. additionThe fractions containing the desired product
  13. concentrationwere concentrated under vacuum
  14. customthen freeze-dried

出典と根拠

ORDレコード
ord-aa0d217a46ef4e929cad61e524395b97
出典データセット
uspto-grants-2012_10
特許番号
US08299063B2

反応ノート

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