Ethanol → 8-methyl-6-(pyridin-4-yl)-9-(tetrahydro-2H-pyran-4-yl)-9H-purin-2-amine

HRID 600415Notes

Reaction equation

HRID 600415 reaction equation
C(O)C.Cl[C:5]1[N:13]=[C:12]([NH2:14])[N:11]=[C:10]2[C:6]=1[N:7]=[C:8]([CH3:21])[N:9]2[CH:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1.[N:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1.C([O-])([O-])=O.[K+].[K+]>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>[CH3:21][C:8]1[N:9]([CH:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[C:10]2[C:6]([N:7]=1)=[C:5]([C:25]1[CH:26]=[CH:27][N:22]=[CH:23][CH:24]=1)[N:13]=[C:12]([NH2:14])[N:11]=2

Participants

7

Reactant 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 576126526-chloro-8-methyl-9-(tetrahydro-2H-pyran-4-yl)-9H-purin-2-amine

Product 1

HCID 576126668-methyl-6-(pyridin-4-yl)-9-(tetrahydro-2H-pyran-4-yl)-9H-purin-2-amineYield 99.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolvent

Conditions

Temperature
150 °C

Procedure

Anhydrous ethanol (4 mL) was added to an argon-purged vial containing 6-chloro-8-methyl-9-(tetrahydro-2H-pyran-4-yl)-9H-purin-2-amine (140 mg, 0.52 mmol), pyridine-4-yl-boronic acid (97 mg, 0.79 mmol, 1.5 equiv.), K2CO3 (109 mg, 0.79 mmol, 1.5 equiv.), and Pd(PPh3)4 (30 mg, 0.026 mmol, 0.05 equiv.) and the mixture was heated for 30 min in the microwave oven at 150° C. After cooling to ambient temperature, the reaction mixture was diluted with methanol (8 mL), filtered through a Nylon 0.45 μm filter and the filtrate concentrated in vacuo. Preparative HPLC purification of the residue afforded, after evaporation and drying, the desired compound as an orange solid (160 mg, 99% yield). TFA salt. 1H NMR (300 MHz, CD3OD) δ, ppm: 9.09 (d, J=6.6 Hz, 2H), 8.95 (d, J=6.2 Hz, 2H), 4.61-4.52 (m, 1H), 4.11 (dd, J=11.5, 4.5 Hz, 2H), 3.61 (app t, J=11.3 Hz, 2H), 2.96-2.82 (m, 2H), 2.68 (s, 3H), 1.84 (dd, J=12.7, 2.3 Hz, 2H); MS (EI) m/z 311.3 (MH)+.

Workup

  1. custompurged vial
  2. temperatureAfter cooling to ambient temperature
  3. filtrationfiltered through a Nylon 0.45 μm
  4. filtrationfilter
  5. concentrationthe filtrate concentrated in vacuo
  6. customPreparative HPLC purification of the residue
  7. customafforded
  8. customafter evaporation
  9. customdrying

Sources & evidence

ORD record
ord-db71339f8f0c4952b3fca9a0a4ea347f
Source dataset
uspto-grants-2011_03
Patent number
US07902187B2

Reaction notes

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