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 1767689ノート

反応式

HRID 1767689 の反応式
[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

参加物

5

反応物 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

生成物 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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

実験手順

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 EtO/Ac/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=/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, 1H), 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]+.

後処理

  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 EtO/Ac/AcOH/H2O 800:55:45)

出典と根拠

ORDレコード
ord-a09831bbb4c2431a91eed0a2230e4970
出典データセット
uspto-grants-2007_06
特許番号
US07235555B2

反応ノート

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