Water → HCID 86669144, compound

HRID 1422661Notes

Reaction equation

HRID 1422661 reaction equation
OC(C)(C)C[C:4]1([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[O:9][C:8](=[O:10])[N:7](C(C2C=CC(B3OC(C)(C)C(C)(C)O3)=CC=2)(C)C)[CH2:6][CH2:5]1.C(=O)([O-])[O-].[Na+].[Na+].O.I[C:45]1[CH:50]=[CH:49][N:48]([CH3:51])[C:47](=[O:52])[CH:46]=1>C1(C)C=CC=CC=1.CCO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:51][N:48]1[CH:49]=[CH:50][CH:45]([CH:6]2[CH2:5][CH:4]([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)[O:9][C:8](=[O:10])[NH:7]2)[CH2:46][C:47]1=[O:52]

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 534080094-Iodo-1-methylpyridin-2(1H)-oneHCID 66869795HCID 66869795, compound

Product 1

HCID 86669144HCID 86669144, compoundYield 60.8%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-(2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-yl)-1,3-oxazinan-2-one (30 mg, 60.9 μmol) in toluene (3 mL) was added a solution of sodium carbonate (64.5 mg, 609 μmol) in EtOH (2 mL)/water (1 mL), 4-iodo-1-methylpyridin-2(1H)-one (14.5 mg, 609 μmol) and Pd(PPh3)4 (7.5 mg, 6 μmol) successively under nitrogen. The mixture was stirred at 100° C. for 2.5 h. The reaction mixture was concentrated under vacuum. The residue was dissolved in water, extracted with EtOAc (5 mL×3). The combined organic layers were dried over Na2SO4, filtered and concentrated under vacuum. The crude product was purified by HPLC to afford 6-(2_hydroxy-2-methylpropyl)-3-(2-(4-(1-methyl-2-oxo-dihydropyridin-4-yl)-6-phenyl-1,3-oxazinan-2-one (10.6 mg, 37%). 1H NMR (CDCl3) δ 7.40-7.19 (m, 8H), 7.09-7.06 (m, 2H), 6.73 (s, 1H), 6.38-6.36 (d, 1H), 3.51 (s, 3H), 3.27-3.24 (m, 1H), 2.85-2.76 (m, 1H), 2.34-2.21 (m, 2H), 2.16 (s, 2H), 1.65-1.53 (d, 3H), 1.45 (s, 3H), 1.08 (s, 3H), 0.96 (s, 3H); LC-MS Method 2 tR=1.05 min, m/z=475.

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. dissolutionThe residue was dissolved in water
  3. extractionextracted with EtOAc (5 mL×3)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe crude product was purified by HPLC

Sources & evidence

ORD record
ord-5930358f2e2c42888697dc69247ffadf
Source dataset
uspto-grants-2015_01
Patent number
US08927539B2

Reaction notes

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