Triethylamine → 7-{6-[(3,3-Dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-3-pyridinyl}-5,7-diazaspiro[3.4]octane-6,8-dione

HRID 527692ノート

反応式

HRID 527692 の反応式
[NH2:1][C:2]1([C:6]([NH:8][C:9]2[CH:10]=[N:11][C:12]([O:15][C:16]3[C:21]4[C:22]([CH3:26])([CH3:25])[CH2:23][O:24][C:20]=4[CH:19]=[CH:18][CH:17]=3)=[CH:13][CH:14]=2)=[O:7])[CH2:5][CH2:4][CH2:3]1.C(N(CC)CC)C.Cl[C:35](Cl)([O:37]C(=O)OC(Cl)(Cl)Cl)Cl>ClCCl>[CH3:25][C:22]1([CH3:26])[C:21]2[C:16]([O:15][C:12]3[N:11]=[CH:10][C:9]([N:8]4[C:6](=[O:7])[C:2]5([CH2:5][CH2:4][CH2:3]5)[NH:1][C:35]4=[O:37])=[CH:14][CH:13]=3)=[CH:17][CH:18]=[CH:19][C:20]=2[O:24][CH2:23]1

参加物

5

反応物 3

HCID 8471TriethylamineHCID 94429Triphosgene2 回HCID 679668331-amino-N-{6-[(3,3-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-3-pyridinyl}cyclobutanecarboxamide2 回

生成物 1

HCID 574102217-{6-[(3,3-Dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-3-pyridinyl}-5,7-diazaspiro[3.4]octane-6,8-dione

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒3 回

反応条件

温度
0 °C

実験手順

1-amino-N-{6-[(3,3-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-3-pyridinyl}cyclobutanecarboxamide (Intermediate 70, 17 mg) was dissolved in dry dichloromethane (1.8 ml). The reaction mixture was cooled down in an ice bath. Triethylamine (39.48 μl, 0.283 mmol) was added at 0° C. Then 0.89 ml of a solution of triphosgene in dry dichloromethane was added dropwise (0.0135 mg, 4.00 mg). The reaction mixture was stirred under argon during 10 min at 0° C., then during 30 min at room temperature. Then an additional 0.25 equivalent of triphosgene in dichloromethane (0.26 M solution) was added at 0° C. and the reaction mixture was stirred under argon an additional 30 min at room temperature. The solvents were removed under vacuum. The residue obtained was purified by flash chromatography on silica gel (Companion system, 4 g silica cartridge) with cyclohexane/ethylacetate as eluents from 100/0 to 55/45. This afforded the title compound (12 mg).

後処理

  1. temperatureThe reaction mixture was cooled down in an ice bath
  2. waitduring 30 min at room temperature
  3. stirringthe reaction mixture was stirred under argon an additional 30 min at room temperature
  4. customThe solvents were removed under vacuum
  5. customThe residue obtained
  6. customwas purified by flash chromatography on silica gel (Companion system, 4 g silica cartridge) with cyclohexane/ethylacetate as eluents from 100/0 to 55/45

出典と根拠

ORDレコード
ord-8236b984068a4aa2995d3af2fe160e2e
出典データセット
uspto-grants-2016_05
特許番号
US09346790B2

反応ノート

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