Cesium carbonate → HCID 59627243, compound

HRID 1523262Notes

Reaction equation

HRID 1523262 reaction equation
[OH:1][C:2]([CH3:35])([CH3:34])[CH2:3][C@:4]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:9][CH2:8][N:7]([C@H:10]([C:12]2[CH:17]=[CH:16][C:15](B3OC(C)(C)C(C)(C)O3)=[CH:14][CH:13]=2)[CH3:11])[C:6](=[O:27])[NH:5]1.I[C:37]1[CH:42]=[CH:41][N:40]([CH3:43])[C:39](=[O:44])[CH:38]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1>[OH:1][C:2]([CH3:34])([CH3:35])[CH2:3][C@:4]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:9][CH2:8][N:7]([C@H:10]([C:12]2[CH:13]=[CH:14][C:15]([C:37]3[CH:42]=[CH:41][N:40]([CH3:43])[C:39](=[O:44])[CH:38]=3)=[CH:16][CH:17]=2)[CH3:11])[C:6](=[O:27])[NH:5]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 534080094-Iodo-1-methylpyridin-2(1H)-oneHCID 59627210HCID 59627210, compound

Product 1

HCID 59627243HCID 59627243, compoundYield 54.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of (S)-4-(2-hydroxy-2-methylpropyl)-4-phenyl-1-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)tetrahydropyrimidin-2(1H)-one (170 mg, 0.36 mmol) and 4-iodo-1-methylpyridin-2(1H)-one (100 mg, 0.43 mmol) in dry 1,4-dioxane (5 mL) was added 2M aq Cs2CO3 (1 mL) and Pd(PPh3)Cl2 (21.4 mg, 0.03 mmol). After addition, the mixture was heated to reflux for 2 h under N2 atmosphere. The solid was filtered off and diluted with water (30 mL) and EtOAc (30 mL). The mixture was extracted with EtOAc (3×40 mL), and the combined organic layer was washed with brine (50 mL), dried over Na2SO4, filtered, and concentrated to dryness. The residue was purified by prep TLC to afford (S)-4-(2-hydroxy-2-methylpropyl)-1-((S)-1-(4-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)phenyl)ethyl)-4-phenyltetrahydropyrimidin-2(1H)-one (90 mg, yield: 54.4%). 1H NMR (CDCl3): 0.661 (s, 3H), 1.23 (s, 3H), 1.49-1.50 (m, 3H), 1.98-2.02 (m, 2H), 2.05-2.13 (m, 1H), 2.17-2.18 (m, 2H), 2.60-2.63 (m, 1H), 2.74-2.78 (m, 1H), 3.57 (s, 3H), 5.87-5.92 (m, 1H), 6.35-6.37 (m, 1H), 6.71-6.72 (d, 1H), 7.18-7.22 (m, 2H), 7.23-7.25 (m, 1H), 7.30-7.32 (m, 2H), 7.33-7.37 (m, 5H).

Workup

  1. additionAfter addition
  2. temperaturethe mixture was heated
  3. temperatureto reflux for 2 h under N2 atmosphere
  4. filtrationThe solid was filtered off
  5. additiondiluted with water (30 mL) and EtOAc (30 mL)
  6. extractionThe mixture was extracted with EtOAc (3×40 mL)
  7. washthe combined organic layer was washed with brine (50 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated to dryness
  11. customThe residue was purified by prep TLC

Sources & evidence

ORD record
ord-01861955a1ba43e68ca00b2daf0fc8e4
Source dataset
uspto-grants-2015_07
Patent number
US09079861B2

Reaction notes

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