HCID 68157070, compound → HCID 178461934, compound

HRID 243444Notes

Reaction equation

HRID 243444 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13]3[CH:14]=[C:15]([F:18])[CH:16]=[CH:17][C:12]=3[N:11]=[C:10]2[C@@H:19]([NH:21][C:22]2[N:30]=[CH:29][N:28]=[C:27]3[C:23]=2[N:24]=[CH:25][N:26]3C2CCCCO2)[CH3:20])[CH:5]=[C:6]([F:8])[CH:7]=1>O1CCOCC1>[F:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13]3[CH:14]=[C:15]([F:18])[CH:16]=[CH:17][C:12]=3[N:11]=[C:10]2[C@@H:19]([NH:21][C:22]2[N:30]=[CH:29][N:28]=[C:27]3[C:23]=2[N:24]=[CH:25][NH:26]3)[CH3:20])[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

3

Reactant 1

HCID 68157070HCID 68157070, compound

Product 1

HCID 178461934HCID 178461934, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of {(S)-1-[1-(3,5-difluorophenyl)-6-fluoro-1H-benzoimidazol-2-yl]ethyl}-[9-(tetrahydropyran-2-yl)-9H-purin-6-yl]amine (137 mg, 0.28 mmol) in 4M HCL in dioxane (10 mL) was stirred for 1 h at RT. The reaction mixture was concentrated in vacuo, diluted with MeOH and loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH, followed by 2M NH3/MeOH. The basic fractions were combined and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PPC, gradient 2.5-10% 2M NH3 in MeOH/DCM) to afford 361 as a white solid (48 mg, 42%). LCMS (Method K): RT 3.65 min [M+H]+ 410. 1H NMR (CDCl3, 400 MHz): δ 12.87 (1H, bs), 8.09-7.94 (3H, m), 7.70 (1H, dd, J=9.0, 5.0 Hz), 7.40-7.38 (2H, m), 7.27-7.23 (1H, m), 7.11 (1H, ddd, J=10.0, 10.0, 2.5 Hz), 7.05-7.02 (1H, m), 5.71-5.61 (1H, m), 1.63 (3H, d, J=7.0 Hz)

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additiondiluted with MeOH
  3. washThe cartridge was washed with MeOH
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified by column chromatography (Si—PPC, gradient 2.5-10% 2M NH3 in MeOH/DCM)

Sources & evidence

ORD record
ord-02eeaba2bfc5424d9ed965ef1ddb0f99
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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