(2S,5R)-1-Boc-2,5-dimethylpiperazine → (2S,5R)-2,5-dimethyl-4-[4-methyl-3-oxo-2-(2-trimethylsilanyl-ethoxymethyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 519192Notes

Reaction equation

HRID 519192 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][C@@H:12]([CH3:14])[NH:11][CH2:10][C@@H:9]1[CH3:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:17]1[CH:18]=[C:19]2[C:28](=[CH:29][CH:30]=1)[O:27][CH2:26][C:25]1[N:20]2[CH:21]([CH3:40])[C:22](=[O:39])[N:23]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[N:24]=1.C(O[Na])(C)(C)C>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:1]([O:5][C:6]([N:8]1[CH2:13][C@@H:12]([CH3:14])[N:11]([C:17]2[CH:18]=[C:19]3[C:28](=[CH:29][CH:30]=2)[O:27][CH2:26][C:25]2[N:20]3[CH:21]([CH3:40])[C:22](=[O:39])[N:23]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:37])([CH3:36])[CH3:38])[N:24]=2)[CH2:10][C@@H:9]1[CH3:15])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 11745988(2S,5R)-1-Boc-2,5-dimethylpiperazineHCID 867274626-Bromo-4-methyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-oneHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 86727608(2S,5R)-2,5-dimethyl-4-[4-methyl-3-oxo-2-(2-trimethylsilanyl-ethoxymethyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl]-piperazine-1-carboxylic acid tert-butyl esterYield 19.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (2S,5R)-2,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester (1.5 g, 7.00 mmol), 6-bromo-4-methyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (Preparation #1, Step E, 1.990 g, 4.67 mmol), Pd(OAc)2 (0.210 g, 0.933 mmol), 2-(dicyclohexylphosphino)-2′,4′,6′-triisoproplylbiphenyl (0.667 g, 1.400 mmol) and t-BuONa (0.897 g, 9.33 mmol) in toluene (120 mL) was heated at 100° C. for 3 h. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 0-50% EtOAc in petroleum ether) to give (2S,5R)-2,5-dimethyl-4-[4-methyl-3-oxo-2-(2-trimethylsilanyl-ethoxymethyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl]-piperazine-1-carboxylic acid tert-butyl ester (0.5 g, 19%) as a solid. LC/MS (Table 1, Method 25) Rt=1.072 min.; MS m/z: 560 [M+H]+.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. concentrationconcentrated in vacuo
  3. customThe residue was purified by column chromatography on silica gel (eluting with 0-50% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-c1a7836fb2454a5b93c59273e1338351
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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