Methanol → N-(2-chloro-4-(3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-ylamino)phenyl)acetamide

HRID 1812067Notes

Reaction equation

HRID 1812067 reaction equation
F[C:2]1[C:7]([C:8]2[N:16]=[C:15]([CH3:17])[N:14]=[C:13]3[C:9]=2[N:10]=[CH:11][N:12]3[CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)=[CH:6][CH:5]=[CH:4][N:3]=1.[NH2:24][C:25]1[CH:30]=[CH:29][C:28]([NH:31][C:32](=[O:34])[CH3:33])=[C:27]([Cl:35])[CH:26]=1.C[Si](N[Si](C)(C)C)(C)C.[Li].CO>C1COCC1.C([O-])(O)=O.[Na+].C(Cl)Cl>[Cl:35][C:27]1[CH:26]=[C:25]([NH:24][C:2]2[C:7]([C:8]3[N:16]=[C:15]([CH3:17])[N:14]=[C:13]4[C:9]=3[N:10]=[CH:11][N:12]4[CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][O:19]3)=[CH:6][CH:5]=[CH:4][N:3]=2)[CH:30]=[CH:29][C:28]=1[NH:31][C:32](=[O:34])[CH3:33]

Participants

8

Reactant 4

HCID 887MethanolHCID 259252N-(4-amino-2-chlorophenyl)acetamideHCID 57426343Lithium bis(trimethylsilyl)amideHCID 595484686-(2-fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

Product 1

HCID 66600017N-(2-chloro-4-(3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-ylamino)phenyl)acetamideYield 79%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
0 °C

Procedure

A glass microwave reaction vessel was charged with 6-(2-fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (100 mg, 0.319 mmol) and N-(4-amino-2-chlorophenyl)acetamide (64.8 mg, 0.351 mmol, Aldrich) in THF (5 mL), argon was bubbled in for 2 min and the tube was sealed. The reaction mixture was cooled to 0° C., lithium bis(trimethylsilyl)amine (1 N in THF,1 mL, 0.957 mmol) was added dropwise. The red solution was stirred at 0° C. for 1 h and then warmed to room temperature. The mixture was diluted with saturated NaHCO3 and extracted with EtOAc (3×).The organic extract was washed with satd. NaCl and dried over Na2SO4. The solution was filtered and concentrated in vacuo. The crude material was purified by chromatography through a Redi-Sep pre-packed silica gel column (25 g) eluting with a gradient of 2% to 5% 2 M NH3.MeOH in DCM to give N-(2-chloro-4-(3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-ylamino)phenyl)acetamide (120 mg, 0.251 mmol, 79% yield) as a yellow solid. 1H NMR (400 MHz, d6-DMSO) δ 12.84 (s, 1H); 9.74 (dd, J=7.92, 1.86 Hz, 1H); 9.47 (s, 1H); 8.89 (s, 1H); 8.42 (dd, J=4.70, 1.76 Hz, 1H); 8.30 (d, J=2.35 Hz, 1H); 7.55-7.63 (m, 1H); 7.45-7.54 (m, 1H); 7.08 (dd, J=7.82, 4.69 Hz, 1H); 5.85 (dd, J=10.95, 2.15 Hz, 1H); 4.01-4.10 (m, 1H); 3.72-3.85 (m, 1H); 2.92 (s, 3H); 2.24-2.39 (m, 1H); 2.08 (s, 3H); 1.96-2.05 (m, 2H); 1.73-1.91 (m, 1H); 1.56-1.70 (m, 2H). m/z (ESI, +ve ion) 478 (M+H)+.

Workup

  1. customA glass microwave reaction vessel
  2. customwas bubbled in for 2 min
  3. customthe tube was sealed
  4. temperaturewarmed to room temperature
  5. extractionextracted with EtOAc (3×
  6. extraction).The organic extract
  7. washwas washed with satd
  8. dry with materialNaCl and dried over Na2SO4
  9. filtrationThe solution was filtered
  10. concentrationconcentrated in vacuo
  11. customThe crude material was purified by chromatography through a Redi-Sep pre-packed silica gel column (25 g)
  12. washeluting with a gradient of 2% to 5% 2 M NH3

Sources & evidence

ORD record
ord-19091a262179481d996653df10c9c5a4
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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