HCID 59605971, compound → HCID 178437409, compound

HRID 1945952Notes

Reaction equation

HRID 1945952 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]([CH:28]5[CH2:33][CH2:32][O:31][CH2:30][CH2:29]5)[CH2:25]4)[N:14]3C3CCCCO3)=[C:10]([N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)[N:9]=2)[C:6]2[CH:40]=[CH:41][CH:42]=[CH:43][C:5]=2[N:4]=1)[CH3:2]>Cl>[NH3:4].[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]([CH:28]5[CH2:29][CH2:30][O:31][CH2:32][CH2:33]5)[CH2:25]4)[NH:14]3)=[C:10]([N:34]3[CH2:35][CH2:36][O:37][CH2:38][CH2:39]3)[N:9]=2)[C:6]2[CH:40]=[CH:41][CH:42]=[CH:43][C:5]=2[N:4]=1)[CH3:2]

Participants

4

Reactant 1

HCID 59605971HCID 59605971, compound

Product 2

HCID 222AmmoniaHCID 178437409HCID 178437409, compoundYield 116.1%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

A mixture of 2-(2-ethylbenzoimidazol-1-yl)-6-morpholin-4-yl-9-(tetrahydropyran-2-yl)-8-[3-(tetrahydropyran-4-yl)azetidin-1-ylmethyl]-9H-purine (0.28 g, 0.48 mmol) in 1.25 M HCl (10 mL) was stirred for 48 h at room temperature. The reaction mixture was concentrated in vacuo. The residue was loaded in MeOH onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH, then the desired product was eluted with DCM, 20-80% MeOH in DCM and 10-40% 2 M NH3 in MeOH in DCM. The residue was purified by flash chromatography (Si—PPC, 2 M NH3 in MeOH:DCM, gradient 0:100 to 4:96) followed by (Si—PPC, 2M NH3 in MeOH:EtOAc, gradient 2.5:97.5 to 10:90 then 2 M NH3 in MeOH:DCM, gradient 2:98 to 10:90) to give 422 as a white solid (0.14 g, 59%). LCMS (Method I): RT=2.50 min, [M+H]+ 503.4. 1H NMR (400 MHz, DMSO-d6): δ 7.96-7.92 (m, 1 H); 7.64-7.60 (m, 1 H); 7.25-7.20 (m, 2 H); 4.28-4.19 (m, 4 H); 3.83 (dd, J=11.3, 4.3 Hz, 2 H); 3.77 (t, J=4.6 Hz, 2 H); 3.72 (s, 2 H); 3.43-3.38 (m, 7 H); 3.27-3.19 (q, J=7.4 Hz, 2 H); 2.96 (t, J=6.9 Hz, 2 H); 2.19-2.11 (m, 1 H); 1.69-1.57 (m, 1 H); 1.50 (d, J=13.0 Hz, 2 H); 1.31 (t, J=7.4 Hz, 3 H); 1.06 (td, J=12.2, 4.3 Hz, 2 H)

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. washThe cartridge was washed with MeOH
  3. washthe desired product was eluted with DCM, 20-80% MeOH in DCM and 10-40% 2 M NH3 in MeOH in DCM
  4. customThe residue was purified by flash chromatography (Si—PPC, 2 M NH3 in MeOH:DCM, gradient 0:100 to 4:96)

Sources & evidence

ORD record
ord-bbc729079e5e40608955fdeea79eddc9
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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