Hydrochloric Acid → HCID 178492204, compound

HRID 510912Notes

Reaction equation

HRID 510912 reaction equation
Br[C:2]1[C:3]([O:28][CH3:29])=[C:4]([CH:10]([NH:12][C:13]2[N:21]=[CH:20][N:19]=[C:18]3[C:14]=2[N:15]=[CH:16][N:17]3C2CCCCO2)[CH3:11])[CH:5]=[C:6]([F:9])[C:7]=1[CH3:8].[CH3:30][S:31]([C:34]1[CH:39]=[CH:38][C:37](B(O)O)=[CH:36][CH:35]=1)(=[O:33])=[O:32].C(=O)([O-])[O-].[K+].[K+].Cl>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.O1CCOCC1.O>[F:9][C:6]1[CH:5]=[C:4]([CH:10]([NH:12][C:13]2[N:21]=[CH:20][N:19]=[C:18]3[C:14]=2[N:15]=[CH:16][NH:17]3)[CH3:11])[C:3]([O:28][CH3:29])=[C:2]([C:37]2[CH:38]=[CH:39][C:34]([S:31]([CH3:30])(=[O:33])=[O:32])=[CH:35][CH:36]=2)[C:7]=1[CH3:8]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 27343644-(Methanesulfonyl)phenylboronic acidHCID 86666828N-[1-(3-Bromo-5-fluoro-2-methoxy-4-methylphenyl)ethyl]-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

Product 1

HCID 178492204HCID 178492204, compoundYield 66%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

N-[1-(3-bromo-5-fluoro-2-methoxy-4-methylphenyl)ethyl]-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (21 mg, 0.044 mmol), [4-(methylsulfonyl)phenyl]boronic acid (13 mg, 0.066 mmol), potassium carbonate (15 mg, 0.11 mmol), water (0.2 mL), and 1,4-dioxane (0.40 mL) were added to a microwave vial. The mixture was degassed under nitrogen for 5 minutes. Tetrakis(triphenylphosphine)palladium(0) (5.1 mg, 4.4 μmol) was added to the mixture and the vial was then sealed and bubbled under nitrogen for 5 minutes. The mixture was heated at 80° C. overnight. The cooled reaction mixture was then treated with 4.0 M hydrogen chloride in water (0.5 mL, 2 mmol) and was stirred at room temperature for 30 minutes. Purification by preparative LCMS (pH 10) RP-HPLC (XBridge C18 Column, eluting with a gradient of acetonitrile in water with 0.2% ammonium hydroxide, at flow rate of 60 mL/min) afforded N-{1-[5-Fluoro-2-methoxy-6-methyl-4′-(methylsulfonyl)biphenyl-3-yl]ethyl}-9H-purin-6-amine (13 mg, 66%). LCMS calculated for C22H23FN5O3S (M+H)+: m/z=456.1. Found: 456.0.

Workup

  1. customThe mixture was degassed under nitrogen for 5 minutes
  2. customthe vial was then sealed
  3. custombubbled under nitrogen for 5 minutes
  4. customThe cooled reaction mixture
  5. customPurification by preparative LCMS (pH 10)
  6. wash(XBridge C18 Column, eluting with a gradient of acetonitrile in water with 0.2% ammonium hydroxide, at flow rate of 60 mL/min)

Sources & evidence

ORD record
ord-f81205f38211453f9fd748b2553c3bec
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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