Potassium Carbonate → HCID 57386410, compound

HRID 1965127Notes

Reaction equation

HRID 1965127 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:11]3([N:15]=[C:14]([NH2:16])[C:13]([CH3:17])=[N:12]3)[CH2:10][CH:9]([CH:18]3[CH2:23][CH2:22][CH2:21][O:20][CH2:19]3)[O:8][C:5]2=[CH:6][CH:7]=1.[Cl:24][C:25]1[CH:26]=[C:27](B(O)O)[CH:28]=[CH:29][CH:30]=1.C([O-])([O-])=O.[K+].[K+].O1CCOCC1>[Cl-].[Na+].O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:24][C:25]1[CH:30]=[C:29]([C:2]2[CH:3]=[C:4]3[C:11]4([N:15]=[C:14]([NH2:16])[C:13]([CH3:17])=[N:12]4)[CH2:10][CH:9]([CH:18]4[CH2:23][CH2:22][CH2:21][O:20][CH2:19]4)[O:8][C:5]3=[CH:6][CH:7]=2)[CH:28]=[CH:27][CH:26]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 2734323(3-Chlorophenyl)boronic acidHCID 57386155HCID 57386155, compound2×

Product 1

HCID 57386410HCID 57386410, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 6-bromo-5′-methyl-2-(tetrahydro-2H-pyran-3-yl)spiro[chroman-4,2′-imidazol]-4′-amine (Isomeric mixture 1 from Example 47 Step 3, 0.181 g, 0.48 mmol), 3-chlorophenylboronic acid (0.112 g, 0.72 mmol), [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride (0.035 g, 0.04 mmol), K2CO3 (2 M aq.) (0.479 mL, 0.96 mmol) and 1,4-dioxane (4 mL) were mixed in a vial and heated in a microwave reactor at 130° C. for 15 min. When cooled to r.t. the mixture was diluted with brine (3 mL) and extracted with DCM (3×3 mL). The combined organics were concentrated and the resulting residue was taken up in MeOH (1.5 mL), filtered and purified by preparative chromatography. The stereoisomers were separated using chiral SFC HPLC on a Phenomenex Lux C4; 4.6*250 mm; 5 μm column, and a mobile phase consisting of 20% MeOH (containing 0.1% diethylamine) and 80% CO2 and a flow rate of 50 mL/min to give:

Workup

  1. additionwere mixed in a vial and
  2. temperatureWhen cooled to r.t. the mixture
  3. extractionextracted with DCM (3×3 mL)
  4. concentrationThe combined organics were concentrated
  5. filtrationfiltered
  6. custompurified by preparative chromatography
  7. customThe stereoisomers were separated
  8. customa flow rate of 50 mL/min to give

Sources & evidence

ORD record
ord-c1ea795a84164b54b4afe3060036a1f1
Source dataset
uspto-grants-2013_04
Patent number
US08415483B2

Reaction notes

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