Hydrochloric Acid → HCID 178437410, compound

HRID 1946176Notes

Reaction equation

HRID 1946176 reaction equation
[CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([CH2:23][N:24]4[CH2:27][CH:26]([N:28]5[CH2:33][CH2:32][NH:31][C:30](=[O:34])[CH2:29]5)[CH2:25]4)[N:14]3C3CCCCO3)=[C:10]([N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)[N:9]=2)[C:6]2[CH:41]=[CH:42][CH:43]=[CH:44][C:5]=2[N:4]=1)[CH3:2].Cl>O1CCOCC1>[CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([CH2:23][N:24]4[CH2:25][CH:26]([N:28]5[CH2:33][CH2:32][NH:31][C:30](=[O:34])[CH2:29]5)[CH2:27]4)[NH:14]3)=[C:10]([N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)[N:9]=2)[C:6]2[CH:41]=[CH:42][CH:43]=[CH:44][C:5]=2[N:4]=1)[CH3:2]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 596060014-{1-[2-(2-Ethylbenzoimidazol-1-yl)-6-morpholin-4-yl-9-(tetrahydropyran-2-yl)-9H-purin-8-ylmethyl]azetidin-3-yl}piperazin-2-one

Product 1

HCID 178437410HCID 178437410, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of 4-{1-[2-(2-ethylbenzoimidazol-1-yl)-6-morpholin-4-yl-9-(tetrahydropyran-2-yl)-9H-purin-8-ylmethyl]azetidin-3-yl}piperazin-2-one (470 mg, 0.78 mmol) in dioxane (20 mL) was added 4M HCl in dioxane (1 mL). The resulting suspension was stirred at r.t for 24 h then the precipitate collected by filtration, washing with dioxane. The resulting solid was partitioned between EtOAc and H2O and the aqueous layer basified to pH 11 with NH4OH. The aqueous phase was neutralised to pH 7 with HCl then loaded onto an Isolute® SCX-2 cartridge which was washed with H2O and MeOH and the product eluted with 2M NH3/MeOH. The resulting residue was purified by column chromatography (C18, MeOH:H2O, 30-95%) then loaded onto an Isolute® SCX-2 cartridge which was washed with H2O and MeOH and the product eluted with 2M NH3/MeOH affording 812 (69 mg, 17%). LCMS (method I): RT 2.16 min, [M+H]+ 517.3. 1H NMR (DMSO, 400 MHz): δ 7.95-7.94 (1 H, m), 7.73 (1 H, s), 7.63-7.62 (1 H, m), 7.25-7.22 (2 H, m), 4.24 (4 H, brd s), 3.79-3.74 (6 H, m), 3.46 (2 H, s), 3.23 (3 H, q, J=7.46 Hz), 3.16-3.04 (5 H, m), 2.84 (2 H, s), 2.45-2.44 (2 H, m), 1.31 (3 H, t, J=7.45 Hz)

Workup

  1. filtrationthe precipitate collected by filtration
  2. washwashing with dioxane
  3. customThe resulting solid was partitioned between EtOAc and H2O
  4. washwas washed with H2O and MeOH
  5. washthe product eluted with 2M NH3/MeOH
  6. customThe resulting residue was purified by column chromatography (C18, MeOH:H2O, 30-95%)
  7. washwas washed with H2O and MeOH
  8. washthe product eluted with 2M NH3/MeOH affording 812 (69 mg, 17%)
  9. customRT 2.16 min, [M+H]+ 517.3

Sources & evidence

ORD record
ord-38855e2d04dc4d4cbd3d40036ad754af
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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