Dabco → 3-(7-{5-[3,4-bis(ethyloxy)phenyl]-1,2,4-oxadiazol-3-yl}-1-methyl-1H-indol-3-yl)propanoic acid

HRID 1512901ノート

反応式

HRID 1512901 の反応式
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:19]=[CH:20][CH:21]=[C:22]4[C:26]=3[NH:25][CH:24]=[C:23]4[CH2:27][CH2:28][C:29]([O:31]CC)=[O:30])[N:14]=2)[CH:7]=[CH:8][C:9]=1[O:10][CH2:11][CH3:12])[CH3:2].[CH2:34]1N2CCN(CC2)C1.C(=O)(OC)OC>CN(C)C=O>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:19]=[CH:20][CH:21]=[C:22]4[C:26]=3[N:25]([CH3:34])[CH:24]=[C:23]4[CH2:27][CH2:28][C:29]([OH:31])=[O:30])[N:14]=2)[CH:7]=[CH:8][C:9]=1[O:10][CH2:11][CH3:12])[CH3:2]

参加物

5

反応物 3

HCID 9237DabcoHCID 12021Dimethyl CarbonateHCID 59146111Ethyl 3-(7-{5-[3,4-bis(ethyloxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoate

生成物 1

HCID 445482253-(7-{5-[3,4-bis(ethyloxy)phenyl]-1,2,4-oxadiazol-3-yl}-1-methyl-1H-indol-3-yl)propanoic acid収率 99.1%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
50 °C

実験手順

Ethyl 3-(7-{5-[3,4-bis(ethyloxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoate (100 mg) (D66), DABCO (13 mg) and N,N-dimethylformamide (4 mL) was added to dimethyl carbonate (10 mL) successively. The reaction vessel was sealed and heated in Biotage Initiator using initial normal to 150° C. for 2 h. After cooling the reaction, the solvent was removed in vacuo. The residue was dissolved in tetrahydrofuran (5 mL) and methanol (5 mL), and then NaOH (27 mg) in water (5 mL) was added. The mixture was stir at 50° C. for 8 h. The organic solvent was evaporated off and the mixture was acidified with HCl (1 M) solution to pH around 1. Extracted with EtOAc (60 mL), the organic layer was separated and the organic solvent was evaporated off. The residue was purified by Mass Directed Auto Prep to afford 3-(7-{5-[3,4-bis(ethyloxy)phenyl]-1,2,4-oxadiazol-3-yl}-1-methyl-1H-indol-3-yl)propanoic acid (E42) (50 mg). δH (DMSO-d6, 400 MHz): 1.35-1.39 (6H, m), 2.61 (2H, t), 2.97 (2H, t), 3.63 (3H, s), 4.12-4.19 (4H, m), 7.15-7.22 (3H, m), 7.43 (1H, dd), 7.65 (1H, d), 7.78 (1H, dd), 7.79 (1H, dd), 12.06 (1H, br s). MS (ES): C24H25N3O5 requires 435; found 436.2 (M+H+).

後処理

  1. customThe reaction vessel was sealed
  2. temperatureheated in Biotage Initiator
  3. customnormal to 150° C.
  4. customfor 2 h
  5. temperatureAfter cooling
  6. customthe reaction
  7. customthe solvent was removed in vacuo
  8. dissolutionThe residue was dissolved in tetrahydrofuran (5 mL)
  9. additionmethanol (5 mL), and then NaOH (27 mg) in water (5 mL) was added
  10. customThe organic solvent was evaporated off
  11. extractionExtracted with EtOAc (60 mL)
  12. customthe organic layer was separated
  13. customthe organic solvent was evaporated off
  14. customThe residue was purified by Mass Directed Auto Prep

出典と根拠

ORDレコード
ord-03efbb96d56448d6ba53671a099b3813
出典データセット
uspto-grants-2012_07
特許番号
US08217028B2

反応ノート

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