Hydrochloric Acid → HCID 67427023, compound

HRID 888971Notes

Reaction equation

HRID 888971 reaction equation
BrC1C=CC=CC=1C1N(C2CCOCC2)C2C(N=1)=C(N1CCN(C)CC1)N=C(C)N=2.CN(C)C=O.[ClH:36].[CH3:37][C:38]1[N:46]=[C:45]2[C:41]([N:42]=[C:43]([C:53]3[CH:60]=[CH:59][CH:58]=[CH:57][C:54]=3[C:55]#[N:56])[N:44]2[CH:47]2[CH2:52][CH2:51][O:50][CH2:49][CH2:48]2)=[C:40]([N:61]2[CH2:66][CH2:65][N:64]([CH3:67])[CH2:63][CH2:62]2)[N:39]=1>C(OCC)C.[C-]#N.[Zn+2].[C-]#N.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>[ClH:36].[CH3:37][C:38]1[N:46]=[C:45]2[C:41]([N:42]=[C:43]([C:53]3[CH:60]=[CH:59][CH:58]=[CH:57][C:54]=3[C:55]#[N:56])[N:44]2[CH:47]2[CH2:52][CH2:51][O:50][CH2:49][CH2:48]2)=[C:40]([N:61]2[CH2:62][CH2:63][N:64]([CH3:67])[CH2:65][CH2:66]2)[N:39]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 59374579HCID 59374579, compoundHCID 67426430HCID 67426430, compound

Product 1

HCID 67427023HCID 67427023, compound

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 3283Diethyl EtherSolvent

Procedure

Charge a microwave reaction vessel with 8-(2-Bromo-phenyl)-2-methyl-6-(4-methyl-piperazin-1-yl)-9-(tetrahydro-pyran-4-yl)-9H-purine (0.0015 mol, 0.7 g), zinc cyanide (0.0022 mol, 0.256 g, 1.5 equiv.), and dry N,N-dimethylformamide (5.0 mL). Degas three times with nitrogen. Add Pd(PPh3)4 (0.0001 mol, 0.17 g, 0.1 equiv.) and degas again three times with nitrogen. Seal the reaction vessel and irradiate at 150° C. for 1 hour in microwave. Cool the reaction mixture to room temperature, quench the reaction mixture with water and extract with ethyl acetate. Wash the organic layer with brine, dry over anhydrous sodium sulfate, filter, and concentrate under reduced pressure to give a residue. Purify the residue on silica gel column eluting with dichloromethane:methanol 99:1 to give the freebase. Add HCl (2M solution in diethyl ether) (0.026 g, 0.0007 mol, 1.0 equiv.) to the mixture of 2-(2-methyl-6-(4-methylpiperazin-1-yl)-9-(tetrahydro-2H-pyran-4-yl)-9H-purin-8-yl)benzonitrile (0.3 g, 0.0007 mol) in diethyl ether (5 mL) at 0° C. and stir for 2 hours at room temperature. Filter the precipitate, wash with diethyl ether, and dry in a vacuum to give the title compound. MS (m/z): 418.29 (M+1).

Workup

  1. additionCharge
  2. customDegas three times with nitrogen
  3. customSeal the reaction vessel
  4. customirradiate at 150° C. for 1 hour in microwave
  5. customquench the reaction mixture with water
  6. extractionextract with ethyl acetate
  7. washWash the organic layer with brine
  8. dry with materialdry over anhydrous sodium sulfate
  9. filtrationfilter
  10. concentrationconcentrate under reduced pressure
  11. customto give a residue
  12. customPurify the residue on silica gel column
  13. washeluting with dichloromethane:methanol 99:1
  14. customto give the freebase
  15. filtrationFilter the precipitate
  16. washwash with diethyl ether
  17. customdry in a vacuum

Sources & evidence

ORD record
ord-819af29daef44303953aa5029058ea32
Source dataset
uspto-grants-2012_08
Patent number
US08252798B2

Reaction notes

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