Acetic Acid → HCID 68728792、化合物

HRID 452999ノート

反応式

HRID 452999 の反応式
[NH2:1][C:2]1[CH:13]=[C:6]2[C:7]([O:9]C(=O)[NH:11][C:5]2=[CH:4][CH:3]=1)=O.C(N(CC)CC)C.[CH2:21]([O:28][CH2:29][C:30](Cl)=[O:31])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.Cl.[NH2:34][CH:35]1[CH2:40][CH2:39][C:38](=[O:41])[NH:37][C:36]1=[O:42].C(O)(=O)C>O>[NH2:11][C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:30](=[O:31])[CH2:29][O:28][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[CH:13][C:6]=1[C:7]([NH:34][CH:35]1[CH2:40][CH2:39][C:38](=[O:41])[NH:37][C:36]1=[O:42])=[O:9]

参加物

7

反応物 5

HCID 176Acetic AcidHCID 8471Triethylamine2 回HCID 1345483-Aminopiperidine-2,6-dione hydrochlorideHCID 177085Benzyloxyacetyl chlorideHCID 27353536-Amino-2-hydroxy-4H-3,1-benzoxazin-4-one

生成物 1

HCID 68728792HCID 68728792、化合物収率 12.2%

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
80 °C

実験手順

To a stirred mixture of 5-amino-isatoic anhydride (1.0 g, 5.6 mmol) and triethyl amine (0.8 mL, 9.0 mmol) in acetronitrile (15 mL), was added benzyloxyacetyl chloride (0.87 mL, 5.6 mmol) dropwise at room temperature. The mixture was kept at room temperature overnight. To the mixture, was added triethylamine (3.1 mL, 22 mmol), 3-amino-piperidine-2,6-dione hydrogen chloride (0.92 g, 5.6 mmol), and acetic acid (3.2 mL, 56 mmol). The mixture was heated at 80° C. for 8 hours. To the mixture, was added water (75 mL). The suspension was filtered and washed with water (75 mL) and ethyl acetate (75 mL) to give a dark solid, which was purified with column chromatography (Silica Gel, methanol/methylene chloride 0% to 10% in 15 min) to give 2-amino-5-(2-benzyloxy-acetylamino)-N-(2,6-dioxo-piperidin-3-yl)-benzamide as a white solid (0.28 g, 12% yield): 1H NMR (DMSO-d6) δ 1.92-2.18 (m, 2H, 2CHH), 2.50-2.55 (m, 1H, CHH), 2.72-2.84 (m, 1H, C H), 4.03 (s, 2H, CH2), 4.61 (s, 2H, CH2), 4.68-4.77 (m, 1H, NCH), 6.19 (br, 2H, NH2), 6.68 (d, J=9 Hz, 1H, Ar), 7.30-7.42 (m, 6H, Ar), 7.62 (d, J=2 Hz, 1H, Ar), 8.43 (d, J=8 Hz, 1H, NH), 9.44 (s, 1H, NH), 10.84 (s, 1H, NH); 13C NMR (DMSO-d6) δ 24.09, 30.96, 49.12, 69.37, 72.35, 114.27, 116.23, 121.11, 125.99, 126.13, 127.64, 127.77, 128.27, 137.68, 146.19, 167.28, 168.36, 172.35, 173.01.

後処理

  1. filtrationThe suspension was filtered
  2. washwashed with water (75 mL) and ethyl acetate (75 mL)
  3. customto give a dark solid, which
  4. customwas purified with column chromatography (Silica Gel, methanol/methylene chloride 0% to 10% in 15 min)

出典と根拠

ORDレコード
ord-9dde7c0582e748e6a1fb6ef6dedb6512
出典データセット
uspto-grants-2013_07
特許番号
US08492395B2

反応ノート

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