Potassium Carbonate → tert-butyl 4-(1-methyl-2-oxo-8-(trifluoromethyl)-3-((2-(trimethylsilyl)ethoxy)methyl)-1,2,3,5-tetrahydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-9-yl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 519098Notes

Reaction equation

HRID 519098 reaction equation
Br[C:2]1[C:3]([C:26]([F:29])([F:28])[F:27])=[CH:4][C:5]2[O:24][CH2:23][C:8]3=[N:9][N:10]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[C:11](=[O:14])[CH:12]([CH3:13])[N:7]3[C:6]=2[CH:25]=1.[C:30]([O:34][C:35]([N:37]1[CH2:42][CH:41]=[C:40](B2OC(C)(C)C(C)(C)O2)[CH2:39][CH2:38]1)=[O:36])([CH3:33])([CH3:32])[CH3:31].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O>[CH3:13][CH:12]1[C:11](=[O:14])[N:10]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[N:9]=[C:8]2[CH2:23][O:24][C:5]3[CH:4]=[C:3]([C:26]([F:29])([F:28])[F:27])[C:2]([C:40]4[CH2:41][CH2:42][N:37]([C:35]([O:34][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:36])[CH2:38][CH:39]=4)=[CH:25][C:6]=3[N:7]12

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 867273036-Bromo-4-methyl-7-trifluoromethyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one

Product 1

HCID 86727470tert-butyl 4-(1-methyl-2-oxo-8-(trifluoromethyl)-3-((2-(trimethylsilyl)ethoxy)methyl)-1,2,3,5-tetrahydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-9-yl)-5,6-dihydropyridine-1(2H)-carboxylateYield 73%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 9-bromo-1-methyl-8-(trifluoromethyl)-3-((2-(trimethylsilyl)ethoxy)methyl)-3,5-dihydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-2(1H)-one (Example #53, Step E, 0.08 g, 0.162 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (0.10 g, 0.324 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II)dichloride dichloromethane complex (0.026 g, 0.032 mmol) and K2CO3 (0.045 g, 0.324 mmol) in dioxane (1.2 mL) and water (0.2 mL) was heated at reflux for 6 h. The reaction mixture was cooled to ambient temperature and filtered. The filtrate was concentrated in vacuo and the residue was purified by column chromatography on silica gel (eluting with 40% EtOAc in petroleum ether) to give tert-butyl 4-(1-methyl-2-oxo-8-(trifluoromethyl)-3-((2-(trimethylsilyl)ethoxy)methyl)-1,2,3,5-tetrahydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-9-yl)-5,6-dihydropyridine-1(2H)-carboxylate (0.07 g, 73%) as a pale-white solid. 1H NMR (methanol-d4, 400 MHz): δ 7.28 (s, 1H), 7.10 (s, 1H), 5.64 (s, 1H), 5.11 (q, J=10.4 Hz, 2H), 4.97 (q, J=6.8 Hz, 1H), 4.69 (d, J=13.2 Hz, 2H), 4.04 (s, 2H), 3.70 (m, 4H), 2.39 (s, 2H), 1.51 (s, 9H), 1.47 (d, J=6.8 Hz, 3H), 0.96 (t, J=8.4 Hz, 2H), 0.00 (s, 9H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 6 h
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated in vacuo
  5. customthe residue was purified by column chromatography on silica gel (eluting with 40% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-0ff526b818054438883893677ae460b4
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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