1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → methyl 3-(7-{5-[3-chloro-4,5-bis(ethyloxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoate

HRID 1512779노트

반응식

HRID 1512779 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([O:14][CH2:15][CH3:16])[C:10]=1[O:11][CH2:12][CH3:13])[C:5]([OH:7])=O.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.O[NH:39]/[C:40](=[N:57]\[H])/[C:41]1[CH:42]=[CH:43][CH:44]=[C:45]2[C:49]=1[NH:48][CH:47]=[C:46]2[CH2:50][CH2:51][C:52]([O:54][CH2:55]C)=[O:53].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[O:7][N:57]=[C:40]([C:41]3[CH:42]=[CH:43][CH:44]=[C:45]4[C:49]=3[NH:48][CH:47]=[C:46]4[CH2:50][CH2:51][C:52]([O:54][CH3:55])=[O:53])[N:39]=2)[CH:8]=[C:9]([O:14][CH2:15][CH3:16])[C:10]=1[O:11][CH2:12][CH3:13]

참가 물질

7

반응물 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 2724141Tetrabutylammonium FluorideHCID 46948803-Chloro-4,5-diethoxybenzoic acidHCID 178506492HCID 178506492, 화합물

생성물 1

HCID 59146107methyl 3-(7-{5-[3-chloro-4,5-bis(ethyloxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoate수율 11.2%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of 3-chloro-4,5-bis(ethyloxy)benzoic acid (D69) (184 mg) in tetrahydrofuran (10 mL) stirred at room temperature was added EDCI (192 mg) and HOBT (153 mg). The reaction mixture was stirred for 2 h, followed by addition of methyl 3-{7-[(Z)-(hydroxyamino)(imino)methyl]-1H-indol-3-yl}propanoate (D35) (131 mg). The reaction mixture was stirred at 60° C. for another 2 h, and then TBAF (523 mg) was added. The reaction vessel was sealed and heated in Biotage Initiator using initial normal to 130° C. for 3 h. After cooling the reaction, the solvent was removed. Water (10 mL) and ethyl acetate (30 mL) was added, the organic layer was separated and the solvent was evaporated off. The residue was purified by Mass Directed Auto Prep to afford methyl 3-(7-{5-[3-chloro-4,5-bis(ethyloxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoate (D70) (25 mg) as a white solid. δH (CDCl3, 400 MHz): 1.46 (3H, t), 1.55 (3H, m), 2.78 (2H, t), 3.18 (2H, t), 3.70 (3H, s), 4.22-4.28 (4H, m), 7.21 (1H, d), 7.29 (1H, t), 7.67 (1H, d), 7.81 (1H, t), 7.93 (1H, d), 8.13 (1H, d), 9.60 (1H, s).

후처리

  1. stirringThe reaction mixture was stirred at 60° C. for another 2 h
  2. customThe reaction vessel was sealed
  3. temperatureheated in Biotage Initiator
  4. customnormal to 130° C.
  5. customfor 3 h
  6. temperatureAfter cooling
  7. customthe reaction
  8. customthe solvent was removed
  9. additionWater (10 mL) and ethyl acetate (30 mL) was added
  10. customthe organic layer was separated
  11. customthe solvent was evaporated off
  12. customThe residue was purified by Mass Directed Auto Prep

출처 및 근거

ORD 기록
ord-bde843e1de44407792c89b093cc64001
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08217028B2

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