Potassium Carbonate → HCID 86727588, compound

HRID 519178Notes

Reaction equation

HRID 519178 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][C:15]=1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[F:22])[O:12][CH2:11][C:10]1[N:5]2[C@H:6]([CH3:24])[C:7](=[O:23])[NH:8][N:9]=1.CC1(C)C(C)(C)OB([C:33]2[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][CH:34]=2)O1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O>[C:42]([O:41][C:39]([N:36]1[CH2:35][CH:34]=[C:33]([C:2]2[CH:3]=[C:4]3[C:13](=[CH:14][C:15]=2[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[F:22])[O:12][CH2:11][C:10]2[N:5]3[C@H:6]([CH3:24])[C:7](=[O:23])[NH:8][N:9]=2)[CH2:38][CH2:37]1)=[O:40])([CH3:45])([CH3:43])[CH3:44]

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 86727587HCID 86727587, compound

Product 1

HCID 86727588HCID 86727588, compoundYield 63.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of (R)-6-bromo-7-(2-fluoro-phenyl)-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (2.0 g, 5.13 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (2.38 g, 7.69 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (0.84 g, 1.03 mmol) and K2CO3 (1.42 g, 10.25 mmol) in dioxane (21 mL) and water (7 mL) was heated at 90° C. overnight. The mixture was cooled to ambient temperature and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 10-50% EtOAc in petroleum ether) to give 4-[(R)-7-(2-fluoro-phenyl)-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (1.6 g, 61%) as a yellow solid. 1H-NMR (400 MHz, CDCl3) δ 8.64 (brs, 1H), 7.36-7.20 (m, 3H), 7.19-7.05 (m, 2H), 6.99 (s, 1H), 6.81 (s, 1H), 5.49 (brs, 1H), 4.79 (q, J=6.4 Hz, 1H), 4.72-4.57 (m, 2H), 3.88 (brs, 2H), 3.35 (m, 2H), 2.06 (brs, 2H), 1.60-1.57 (m, 3H), 1.47 (s, 9H).

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. concentrationconcentrated in vacuo
  3. customThe residue was purified by column chromatography on silica gel (eluting with 10-50% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-3923820383c24b21a95905017286d9c1
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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