Sodium Carbonate → HCID 50905956, compound

HRID 1422662Notes

Reaction equation

HRID 1422662 reaction equation
[OH:1][C:2]([CH3:36])([CH3:35])[CH2:3][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:11]([CH3:28])([C:13]2[CH:18]=[CH:17][C:16](B3OC(C)(C)C(C)(C)O3)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1.C(=O)([O-])[O-].[Na+].[Na+].[CH:43]1([N:46]2[CH:51]=[CH:50][C:49](I)=[CH:48][C:47]2=[O:53])[CH2:45][CH2:44]1>COCCOC.CCO.O.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>[CH:43]1([N:46]2[CH:51]=[CH:50][C:49]([C:16]3[CH:15]=[CH:14][C:13]([C:11]([N:7]4[CH2:6][CH2:5][C:4]([CH2:3][C:2]([OH:1])([CH3:36])[CH3:35])([C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=5)[O:9][C:8]4=[O:10])([CH3:12])[CH3:28])=[CH:18][CH:17]=3)=[CH:48][C:47]2=[O:53])[CH2:45][CH2:44]1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 591903761-cyclopropyl-4-iodopyridin-2(1H)-oneHCID 66869795HCID 66869795, compound

Product 1

HCID 50905956HCID 50905956, compoundYield 112.2%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 6-(2-Hydroxy-2-methyl-propyl)-3-{1-methyl-1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-ethyl}-6-phenyl-[1,3]oxazinan-2-one (50 mg, 151.5 μmol) in DME (10 mL) were added a solution of sodium carbonate (64.5 mg, 609 μmol) in EtOH (2 mL) and water (1 mL), 1-cyclopropyl-4-iodo-1H-pyridin-2-one (19 mg, 73 μmol) and Pd(PPh3)4(7.5 mg, 6 μmol) successively under nitrogen. The reaction mixture was stirred at 100° C. for 2.5 h and then 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 preparative prep HPLC to afford 3-{1-[4-(1-Cyclopropyl-2-oxo-1,2-dihydro-pyridin-4-yl)-phenyl]-1-methyl-ethyl}-6-(2-hydroxy-2-methyl-propyl)-6-phenyl-[1,3]oxazinan-2-one (41 mg, 71%). 1H NMR (CDCl3) δ 7.45-7.25 (m, 8H), 7.12-7.10 (d, 2H), 6.75 (s, 1H), 6.40 (d, 1H), 3.39-3.29 (m, 2H), 2.90-2.83 (m, 1H), 2.39-2.21 (m, 4H), 1.67 (d, 3H), 1.50 (s, 3H), 1.16-1.12 (m, 5H), 1.02 (s, 3H), 0.92-0.87 (m, 2H); LC-MS Method 2 tR=1.10 min, m/z=501.

Workup

  1. concentrationconcentrated 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 preparative prep HPLC

Sources & evidence

ORD record
ord-5e49fd92d5a74c3e880c42d0be96e218
Source dataset
uspto-grants-2015_01
Patent number
US08927539B2

Reaction notes

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