Sodium Carbonate → HCID 90426130, compound

HRID 527464Notes

Reaction equation

HRID 527464 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C@@H:9]2[CH2:13][CH2:12][O:11][CH2:10]2)[C:5]([CH3:14])=[C:4]([Cl:15])[N:3]=1.C([O-])([O-])=O.[Na+].[Na+].[OH:22][C:23]1[CH:24]=[C:25](B(O)O)[CH:26]=[CH:27][CH:28]=1>O1CCOCC1.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>[Cl:15][C:4]1[C:5]([CH3:14])=[C:6]([NH:8][C@@H:9]2[CH2:13][CH2:12][O:11][CH2:10]2)[N:7]=[C:2]([C:27]2[CH:28]=[C:23]([OH:22])[CH:24]=[CH:25][CH:26]=2)[N:3]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2734359(3-hydroxyphenyl)boronic AcidHCID 90426233(R)-2,6-dichloro-5-methyl-N-(tetrahydrofuran-3-yl)pyrimidin-4-amine

Product 1

HCID 90426130HCID 90426130, compoundYield 107.5%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (R)-2,6-dichloro-5-methyl-N-(tetrahydrofuran-3-yl)pyrimidin-4-amine (1.8 g, 7.3 mmol) in degassed dioxane and H2O (4/1, 21 mL) was added Na2CO3 (1.5 g, 14.5 mmol); Pd(PPh3)4 (296 mg, 0.36 mmol) and 3-hydroxy-phenylboronic acid (1.21 g, 8.8 mmol). The system was purged with nitrogen stream and then stirred at 100° C. for 14 h., cooled down to room temperature, diluted with water (30 mL) and the resulting mixture extracted with EtOAc (30 mL×2). The combined organic layer were dried over Na2SO4, filtered and concentrated. The residue was purified by chromatographic column on silica gel (EtOAc/petroleum ether, gradient elution, from 1/10 to 2:1) to give (R)-3-(4-chloro-5-methyl-6-(tetrahydrofuran-3-ylamino)pyrimidin-2-yl)phenol (2.4 g, 33%) as a white solid. ESI-LCMS (m/z): 306.1 [M+1]+.

Workup

  1. customThe system was purged with nitrogen stream
  2. temperaturecooled down to room temperature
  3. additiondiluted with water (30 mL)
  4. extractionthe resulting mixture extracted with EtOAc (30 mL×2)
  5. dry with materialThe combined organic layer were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by chromatographic column on silica gel (EtOAc/petroleum ether, gradient elution, from 1/10 to 2:1)

Sources & evidence

ORD record
ord-c8046c2a6a4c4cb6b7ec7a45303510dd
Source dataset
uspto-grants-2016_05
Patent number
US09346802B2

Reaction notes

Loading…