Cesium carbonate → HCID 86719344, compound

HRID 1519424Notes

Reaction equation

HRID 1519424 reaction equation
Br[C:2]1[N:7]=[C:6]([CH2:8][OH:9])[CH:5]=[CH:4][C:3]=1[O:10][CH2:11][CH2:12][O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15].[CH:21]([N:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1)([CH3:23])[CH3:22].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>[Cl-].[Na+].O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Si:14]([O:13][CH2:12][CH2:11][O:10][C:3]1[CH:4]=[CH:5][C:6]([CH2:8][OH:9])=[N:7][C:2]=1[N:27]1[CH2:28][CH2:29][N:24]([CH:21]([CH3:23])[CH3:22])[CH2:25][CH2:26]1)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 780131-IsopropylpiperazineHCID 634876Binap, (A+-)-HCID 86719024HCID 86719024, compound

Product 1

HCID 86719344HCID 86719344, compoundYield 44%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of (6-bromo-5-(2-((tert-butyldimethylsilyl)oxy)ethoxy)pyridin-2-yl)methanol (2.18 g, 6.0 mmol), 1-isopropylpiperazine (0.92 g, 7.2 mmol), BINAP (0.37 g, 0.6 mmol), and Cs2CO3 (3.18 g, 9.0 mmol) in nitrogen saturated toluene (40 mL) was added palladium(II) acetate (0.13 g, 0.6 mmol). The resulting mixture was heated at 100° C. for 18 h. After that time the reaction was cooled to rt, diluted with brine and extracted with ethyl acetate. The organic phase was dried over Na2SO4 and concentrated under reduced pressure. The product was purified by flash column chromatography (silica gel, 95:5 dichloromethane/methanol to 90:10 dichloromethane/methanol) to give (5-(2-((tert-butyldimethylsilyl)oxy)ethoxy)-6-(4-isopropylpiperazin-1-yl)pyridin-2-yl)methanol (1.07 g, 44%) as a sticky yellow solid: 1H NMR (400 MHz, CDCl3): δ 7.05 (d, J=7.6 Hz, 1H), 6.66 (d, J=8.0 Hz, 1H), 4.59 (s, 2H), 4.06-3.97 (m, 4H), 3.53 (br s, 4H), 2.68 (m, 5H), 1.10 (d, J=6.4 Hz, 6H), 0.90 (s, 9H), 0.09 (s, 6H).

Workup

  1. temperatureAfter that time the reaction was cooled to rt
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic phase was dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe product was purified by flash column chromatography (silica gel, 95:5 dichloromethane/methanol to 90:10 dichloromethane/methanol)

Sources & evidence

ORD record
ord-683e239bfe3147a9979badf0fc24689d
Source dataset
uspto-grants-2015_07
Patent number
US09073878B2

Reaction notes

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