Dimethylformamide → HCID 178461917, compound

HRID 243405Notes

Reaction equation

HRID 243405 reaction equation
Br[C:2]1[C:7]2[N:8]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[C:9]([C@@H:11]([NH:13][C:14]3[N:22]=[CH:21][N:20]=[C:19]4[C:15]=3[N:16]=[CH:17][N:18]4C3CCCCO3)[CH3:12])=[N:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.[CH3:35][N:36](C=O)C>C(Cl)Cl.[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>[C:29]1([N:8]2[C:7]3[C:2]([C:35]#[N:36])=[CH:3][CH:4]=[CH:5][C:6]=3[N:10]=[C:9]2[C@@H:11]([NH:13][C:14]2[N:22]=[CH:21][N:20]=[C:19]3[C:15]=2[N:16]=[CH:17][NH:18]3)[CH3:12])[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 68157574HCID 68157574, compound

Product 1

HCID 178461917HCID 178461917, compoundYield 73%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
150 °C

Procedure

[(S)-1-(7-Bromo-1-phenyl-1H-benzoimidazol-2-yl)ethyl][9-(tetrahydropyran-2-yl)-9H-purin-6-yl]amine (300 mg, 0.58 mmol) was dissolved in DMF (1 mL) in a microwave vial and zinc cyanide (68 mg, 0.58 mmol) and Pd(PPh3)4 (67 mg, 0.058 mmol) added. The vial was sealed and evacuated and purged with argon (×3). The vial was heated at 150° C. by microwave irradiation for 15 min. The resulting colourless solution was poured onto a mixture of EtOAc and water. A white solid precipitated and was dispersed between the 2 phases. The solid was isolated by filtration and dissolved in DCM and the resulting solution washed with NaHCO3 (satd. aq. soln.). The DCM fraction was passed through a PTFE cartridge. The DCM was removed in vacuo and the residue purified by passage through an SCX cartridge. The cartridge was washed with MeOH and the product eluted with 2M NH3 in MeOH. The product fractions were combined and evaporated and the residue purified by chromatography (Si—PCC) eluting with 0-8% MeOH in DCM. The product fractions were concentrated in vacuo to give white solid. This was triturated in ether, filtered and dried in vacuo to give 279 as a white solid (160 mg, 73%). 1H NMR (DMSO-d6, 400 MHz) δ: 8.09 (1H, br s), 8.03 (1H, s), 7.98 (2H, d, J=8.2 Hz), 7.66-7.59 (3H, m), 7.56-7.37 (4H, m), 7.33 (1H, t, J=7.9 Hz), 5.35-5.21 (1H, m), 1.54 (3H, d, J=6.9 Hz). LCMS (Method K): RT 3.07 min; m/z 381 [M+H]+

Workup

  1. additionadded
  2. customThe vial was sealed
  3. customevacuated
  4. custompurged with argon (×3)
  5. additionThe resulting colourless solution was poured onto a mixture of EtOAc and water
  6. customA white solid precipitated
  7. additionwas dispersed between the 2 phases
  8. customThe solid was isolated by filtration
  9. washthe resulting solution washed with NaHCO3 (satd. aq. soln.)
  10. customThe DCM was removed in vacuo
  11. customthe residue purified by passage through an SCX cartridge
  12. washThe cartridge was washed with MeOH
  13. washthe product eluted with 2M NH3 in MeOH
  14. customevaporated
  15. customthe residue purified by chromatography (Si—PCC)
  16. washeluting with 0-8% MeOH in DCM
  17. concentrationThe product fractions were concentrated in vacuo
  18. customto give white solid
  19. customThis was triturated in ether
  20. filtrationfiltered
  21. customdried in vacuo

Sources & evidence

ORD record
ord-cf301291dd5746808c44146db8a383ba
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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