Formic Acid → (1R,5R,6S)-6-[4-(4-Amino-5-oxo-7,8-dihydro-5H-9-oxa-1,3,6-triaza-benzo cyclohepten-6-yl)-phenyl]-tricyclo[3.2.1.0*2,4*]octane-3-carboxylic Acid Methyl Ester

HRID 2237636ノート

反応式

HRID 2237636 の反応式
[NH2:1][C:2]1[C:7]2[C:8](=[O:20])[N:9]([C:13]3[CH:18]=[CH:17][C:16](I)=[CH:15][CH:14]=3)[CH2:10][CH2:11][O:12][C:6]=2[N:5]=[CH:4][N:3]=1.[CH2:21]([O:23][C:24]([CH:26]([CH2:29][CH2:30][CH:31]=[CH:32][CH3:33])[CH2:27]C)=[O:25])C.N1CCCC[CH2:35]1.C(O)=O>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C.C(Cl)(Cl)Cl.CO.CCOC(C)=O>[CH3:21][O:23][C:24]([CH:26]1[CH:27]2[CH:29]1[C@@H:30]1[CH2:31][C@H:32]2[C@@H:33]([C:16]2[CH:17]=[CH:18][C:13]([N:9]3[CH2:10][CH2:11][O:12][C:6]4[N:5]=[CH:4][N:3]=[C:2]([NH2:1])[C:7]=4[C:8]3=[O:20])=[CH:14][CH:15]=2)[CH2:35]1)=[O:25]

参加物

10

反応物 4

HCID 284Formic AcidHCID 8082PiperidineHCID 593025304-Amino-6-(4-iodophenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-oneHCID 131728124Oct-6-ene-3-carboxylic acid ethyl ester

生成物 1

HCID 59302525(1R,5R,6S)-6-[4-(4-Amino-5-oxo-7,8-dihydro-5H-9-oxa-1,3,6-triaza-benzo cyclohepten-6-yl)-phenyl]-tricyclo[3.2.1.0*2,4*]octane-3-carboxylic Acid Methyl Ester

試薬・触媒・溶媒 5

HCID 67553Tetrabutylammonium Iodide触媒HCID 887Methanol溶媒HCID 6212Chloroform溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

The named was prepared as follows. A slurry of 4-amino-6-(4-iodophenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one (340 mg, 0.89 mmol), tricycle[3.2.1.0*2,4*]oct-6-ene-3-carboxylic acid ethyl ester (240 mg, 1.35 mmol), tetrabutylammonium iodide (67 mg, 0.18 mmol), piperidine (230 mg, 2.7 mmol), formic acid (170 mg, 0.14 mmol) and dichlorobis(acetonitrile) palladium(II) (23 mg, 0.09 mmol) in DMF (0.36 mL) was stirred at 125° C. for 16 hours. The reaction mixture was cooled, diluted into EtOAc, washed with water, saturated aqueous brine, dried over magnesium sulfate and concentrated in vacuo to afford an oil. Chromatography (20 g of silica gel, 1-5% methanol:chloroform) afforded a solid, 127 mg. IC50 78.3 nM.

後処理

  1. customThe named was prepared
  2. temperatureThe reaction mixture was cooled
  3. washwashed with water, saturated aqueous brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customto afford an oil

出典と根拠

ORDレコード
ord-4c9057a628154627ba342972ca859969
出典データセット
uspto-grants-2010_05
特許番号
US07718645B2

反応ノート

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