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 2237636노트

반응식

HRID 2237636 반응식
[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]

참가 물질

10

반응물 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

생성물 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

시약·촉매·용매 5

HCID 67553Tetrabutylammonium Iodide촉매HCID 887Methanol용매HCID 6212Chloroform용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-4c9057a628154627ba342972ca859969
출처 데이터셋
uspto-grants-2010_05
특허 번호
US07718645B2

반응 노트

불러오는 중…