Hydrochloric Acid → 3-Pyridin-3-ylmethylene-5-(3,4,5-trimethoxy-phenyl)-1,3-dihydro-pyrrolo[2,3-b]pyridin-2-one

HRID 85043

反応式

HRID 85043 の反応式
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:13]2[CH:14]=[C:15]3[CH2:21][C:20](=O)[N:19]([CH2:23][O:24]CC[Si](C)(C)C)[C:16]3=[N:17][CH:18]=2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].C(N(CC)CC)C.[N:38]1[CH:43]=[CH:42][CH:41]=[C:40](C=O)[CH:39]=1.Cl>C1(C)C=CC=CC=1.CO>[N:38]1[CH:43]=[CH:42][CH:41]=[C:40]([CH:20]=[C:21]2[C:15]3[C:16](=[N:17][CH:18]=[C:13]([C:5]4[CH:6]=[C:7]([O:11][CH3:12])[C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=4)[CH:14]=3)[NH:19][C:23]2=[O:24])[CH:39]=1

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 103713-PyridinecarboxaldehydeHCID 667788935-(3,4,5-Trimethoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1,3-dihydro-pyrrolo[2,3-b]pyridin-2-one

生成物 1

HCID 667792563-Pyridin-3-ylmethylene-5-(3,4,5-trimethoxy-phenyl)-1,3-dihydro-pyrrolo[2,3-b]pyridin-2-one収率 72%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 1140Toluene溶媒

実験手順

To a solution of 5-(3,4,5-trimethoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1,3-dihydro-pyrrolo[2,3-b]pyridin-2-one (157 mg, 0.365 mmol) in toluene (2 mL) was added triethylamine (56 μl, 0.365 mmol), molecular sieves 4 Å (100 mg), and 3-pyridinecarboxaldehyde (38 μl, 0.401 mmol). The resulting mixture was stirred overnight at room temperature, after which it was filtered and partitioned between DCM and H2O. The organic layer was separated, dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography eluting with 40-70% EtOAc:Hexanes to yield the SEM-protected precursor as a mixture of cis and trans isomers (101 mg, 53%). 41 mg (0.079 mmol) of this material was dissolved in MeOH (1.5 ml), 6 N HCl (3 ml) was added, and the mixture was stirred for 3 hours at 45° C. The reaction was quenched with 1 N NaOH (15 ml), neutralized by the addition of saturated NaHCO3 and extracted with DCM. Silica gel chromatography eluting with 0-5% MeOH:DCM yielded the title compound (22 mg, 72%) as a cis/trans-mixture. 1H NMR (CDCl3, 300 MHz): δ 9.15 (d, J=4.8 Hz, 1H), 9.11 (bs, 1H), 9.02 (d, J=1.2 Hz, 1H), 8.98 (d, J=1.1, 1H), 8.69 (dd, J=0.9, 2.9 Hz, 1H), 8.66 (dd, J=0.9, 2.8 Hz, 1H), 8.39 (d, J=1.2 Hz, 1H), 8.37 (d, J=1.2 Hz, 1H), 7.95 (m, 1H), 7.93 (s, 1H), 7.87 (d, J=1.1 Hz, 1H), 7.44 (m, 1H), 6.75 (s, 2H), 6.59 (s, 2H), 3.97 (s, 6H), 3.91 (s, 3H), 3.90 (s, 6H), 3.86 (s, 3H).

後処理

  1. filtrationafter which it was filtered
  2. custompartitioned between DCM and H2O
  3. customThe organic layer was separated
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with 40-70% EtOAc
  9. customHexanes to yield the SEM-protected precursor
  10. additionas a mixture of cis and trans isomers (101 mg, 53%)
  11. stirringthe mixture was stirred for 3 hours at 45° C
  12. customThe reaction was quenched with 1 N NaOH (15 ml)
  13. additionneutralized by the addition of saturated NaHCO3
  14. extractionextracted with DCM
  15. washSilica gel chromatography eluting with 0-5% MeOH

出典と根拠

ORDレコード
ord-6f89cb42d5874a0fb2923e8eb80cf468
出典データセット
uspto-grants-2014_09
特許番号
US08846909B2

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