Potassium Carbonate → (E)-tert-butyl 3-((8-(2-ethoxyvinyl)-1-methyl-2-oxo-1,2,3,5-tetrahydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-9-yl)amino)azetidine-1-carboxylate

HRID 519062Notes

Reaction equation

HRID 519062 reaction equation
Br[C:2]1[C:17]([NH:18][CH:19]2[CH2:22][N:21]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:20]2)=[CH:16][C:5]2[N:6]3[CH:11]([CH3:12])[C:10](=[O:13])[NH:9][N:8]=[C:7]3[CH2:14][O:15][C:4]=2[CH:3]=1.[CH2:30]([O:32]/[CH:33]=[CH:34]/B1OC(C)(C)C(C)(C)O1)[CH3:31].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[CH2:33]([O:32]/[CH:30]=[CH:31]/[C:2]1[C:17]([NH:18][CH:19]2[CH2:20][N:21]([C:23]([O:25][C:26]([CH3:28])([CH3:27])[CH3:29])=[O:24])[CH2:22]2)=[CH:16][C:5]2[N:6]3[CH:11]([CH3:12])[C:10](=[O:13])[NH:9][N:8]=[C:7]3[CH2:14][O:15][C:4]=2[CH:3]=1)[CH3:34]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 219739081-Ethoxyethene-2-boronic acid pinacol esterHCID 867272933-(7-Bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 86727429(E)-tert-butyl 3-((8-(2-ethoxyvinyl)-1-methyl-2-oxo-1,2,3,5-tetrahydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-9-yl)amino)azetidine-1-carboxylateYield 51%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of tert-butyl 3-((8-bromo-1-methyl-2-oxo-1,2,3,5-tetrahydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-9-yl)amino)azetidine-1-carboxylate (Example 1, Step B, 0.20 g, 0.43 mmol), (E)-2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.1 g, 0.5 mmol) in dioxane (6 mL) and water (1 mL) was added PdCl2(dppf)-CH2Cl2 adduct (0.035 g, 0.043 mmol) and K2CO3 (0.118 g, 0.85 mmol). The reaction mixture was stirred at 100° C. overnight. The reaction mixture was cooled to ambient temperature, the solvent was removed in vacuo and the residue was purified by chromatography on silica gel (eluting with 2% MeOH in DCM) to give (E)-tert-butyl 3-((8-(2-ethoxyvinyl)-1-methyl-2-oxo-1,2,3,5-tetrahydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-9-yl)amino)azetidine-1-carboxylate (0.10 g, 51%) as a yellow solid. LC/MS (Table 1, Method 2) Rt=1.352 min.; MS m/z: 458 [M+H]+.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. customthe solvent was removed in vacuo
  3. customthe residue was purified by chromatography on silica gel (eluting with 2% MeOH in DCM)

Sources & evidence

ORD record
ord-4eec6d78a3054aa0ba84a9e27bf51d06
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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