2-(1-Methyl-1H-indol-3-YL)-2-oxoacetic acid methyl ester → 3-[3-(4,7-Diaza-spiro[2.5]oct-7-yl)-naphthalen-1-yl]-4-(1-methyl-1H-indol-3-yl)-pyrrole-2,5-dione

HRID 900145노트

반응식

HRID 900145 반응식
[CH2:1]1[C:3]2([CH2:8][N:7]([C:9]3[CH:10]=[C:11]([CH2:19][C:20]([NH2:22])=[O:21])[C:12]4[C:17]([CH:18]=3)=[CH:16][CH:15]=[CH:14][CH:13]=4)[CH2:6][CH2:5][NH:4]2)[CH2:2]1.C[O:24][C:25](=O)[C:26]([C:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[N:30]([CH3:37])[CH:29]=1)=O.CC([O-])(C)C.[K+]>C1COCC1>[CH2:2]1[C:3]2([CH2:8][N:7]([C:9]3[CH:10]=[C:11]([C:19]4[C:20](=[O:21])[NH:22][C:25](=[O:24])[C:26]=4[C:28]4[C:36]5[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=5)[N:30]([CH3:37])[CH:29]=4)[C:12]4[C:17]([CH:18]=3)=[CH:16][CH:15]=[CH:14][CH:13]=4)[CH2:6][CH2:5][NH:4]2)[CH2:1]1

참가 물질

5

반응물 3

HCID 44536752-(1-Methyl-1H-indol-3-YL)-2-oxoacetic acid methyl esterHCID 211145032-[3-(4,7-Diaza-spiro[2.5]oct-7-yl)-naphthalen-1-yl]-acetamideHCID 23665647Potassium tert-butoxide

생성물 1

HCID 211145053-[3-(4,7-Diaza-spiro[2.5]oct-7-yl)-naphthalen-1-yl]-4-(1-methyl-1H-indol-3-yl)-pyrrole-2,5-dione

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

실험 절차

2-[3-(4,7-Diaza-spiro[2.5] oct-7-yl)-naphthalen-1-yl]-acetamide (100 mg, 0.30 mmol) and (1-methyl-1H-indol-3-yl)-oxo-acetic acid methyl ester (97 mg, 0.44 mmol) are azeotroped three times with dry THF and then dissolved in dry THF (3 ml). A solution of 1.0 M KOtBu in THF (1.2 ml) is added dropwise over 20 minutes at RT. After 5 minutes, TLC analysis indicates complete conversion of starting materials. The reaction is quenched by the additon of water (5 ml). The mixture is diluted with EtOAc and washed twice with saturated aq. NH4Cl. The aqueous layers are back extracted twice with EtOAc. The combined organic layers are dried over Na2SO4 and the solvent is evaporated. The residue is purified by FCC (EtOAc/AcOH/H2O 800:55:45) to afford the title compound as its acetate salt. The compound is dissolved in MeOH/TFA and the solvent is removed to yield the title compound as its trifluoroacetate salt. 1H NMR (DMSO, 400 MHz) δ 0.95 (M, 4H), 3.39 (br, 4H), 3.49 (br, 2H), 3.86 (s, 3H), 6.16 (d, J=7.9 Hz, 1H), 6.46 (dd, J=6.6/7.9 Hz, 1H), 7.00 (dd, J=6.6/7.9 Hz, 1H), 7.13 (dd, J=7.6/7.6 Hz, 1H), 7.40 (m, 4H), 7.55 (d, J=8.5 Hz, 1 H), 7.78 (d, J=7.6 Hz, 1H), 8.14 (s, 1H), 9.10 (br, 2H), 11.17 (s, 1H); ES-MS: 463 [M+H]+.

후처리

  1. customThe reaction is quenched by the additon of water (5 ml)
  2. additionThe mixture is diluted with EtOAc
  3. washwashed twice with saturated aq. NH4Cl
  4. extractionThe aqueous layers are back extracted twice with EtOAc
  5. dry with materialThe combined organic layers are dried over Na2SO4
  6. customthe solvent is evaporated
  7. customThe residue is purified by FCC (EtOAc/AcOH/H2O 800:55:45)

출처 및 근거

ORD 기록
ord-d742cfbbd7a1481d96fe110deeb3f771
출처 데이터셋
uspto-grants-2008_04
특허 번호
US07358253B2

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