Hydrochloric Acid → HCID 178486721, compound

HRID 510919Notes

Reaction equation

HRID 510919 reaction equation
Br[C:2]1[C:3]([O:27][CH3:28])=[C:4]([CH:9]([NH:11][C:12]2[N:20]=[CH:19][N:18]=[C:17]3[C:13]=2[N:14]=[CH:15][N:16]3C2CCCCO2)[CH3:10])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[Cl:29][C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[N:34][CH:35]=1.C(=O)([O-])[O-].[K+].[K+].Cl>O.O1CCOCC1.CO.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:8][C:6]1[CH:7]=[C:2]([C:32]2[CH:33]=[N:34][CH:35]=[C:30]([Cl:29])[CH:31]=2)[C:3]([O:27][CH3:28])=[C:4]([CH:9]([NH:11][C:12]2[N:20]=[CH:19][N:18]=[C:17]3[C:13]=2[N:14]=[CH:15][NH:16]3)[CH3:10])[CH:5]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 201118775-Chloropyridine-3-boronic acidHCID 67969174N-[1-(3-Bromo-5-chloro-2-methoxyphenyl)ethyl]-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

Product 1

HCID 178486721HCID 178486721, compoundYield 15.1%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of N-[1-(3-bromo-5-chloro-2-methoxyphenyl)ethyl]-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (45 mg, 0.096 mmol) and (5-chloropyridin-3-yl)boronic acid (23 mg, 0.15 mmol) in water (0.5 mL) and 1,4-dioxane (1 mL) was treated with potassium carbonate (33 mg, 0.24 mmol) and tetrakis(triphenylphosphine)palladium(0) (11 mg, 9.6 mmol). The reaction mixture was degassed with nitrogen for 5 min and heated at 80° C. overnight. The reaction mixture was cooled treated directly with 6 M hydrogen chloride in water (170 μL, 1.0 mmol) and stirred at room temperature for ˜30 minutes. The reaction mixture was diluted slightly with methanol, filtered, and directly purified via preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) to give the desired product (6 mg, 15%). LCMS for C19H17Cl2N6O (M+H)+: m/z=415.1. Found: 415.0; 1H NMR (300 MHz, DMSO-d6): δ 8.72 (d, J=1.8 Hz, 1H), 8.66 (d, J=2.3 Hz, 1H), 8.20-8.09 (m, 4H), 7.65 (d, J=2.1 Hz, 1H), 7.40 (d, J=2.6 Hz, 1H), 5.91-5.71 (m, 1H), 3.52 (s, 3H), 1.51 (d, J=7.0 Hz, 3H).

Workup

  1. customThe reaction mixture was degassed with nitrogen for 5 min
  2. temperatureThe reaction mixture was cooled
  3. filtrationfiltered
  4. customdirectly purified via preparative LCMS (XBridge C18 column
  5. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

Sources & evidence

ORD record
ord-3a1d7e9735304e12948ace6371856d23
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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