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 2237636Notes

Reaction equation

HRID 2237636 reaction equation
[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]

Participants

10

Reactant 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

Product 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

Reagents, catalysts & solvents 5

HCID 67553Tetrabutylammonium IodideCatalystHCID 887MethanolSolventHCID 6212ChloroformSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-4c9057a628154627ba342972ca859969
Source dataset
uspto-grants-2010_05
Patent number
US07718645B2

Reaction notes

Loading…