1,2-Dichloroethane → 4-(1-((2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)azetidin-3-yl)piperazin-2-one

HRID 1946021Notes

Reaction equation

HRID 1946021 reaction equation
[CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([CH:18]=O)[N:14]3[CH3:17])=[C:10]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)[N:9]=2)[C:6]2[CH:26]=[CH:27][CH:28]=[CH:29][C:5]=2[N:4]=1)[CH3:2].[NH:30]1[CH2:33][CH:32]([N:34]2[CH2:39][CH2:38][NH:37][C:36](=[O:40])[CH2:35]2)[CH2:31]1.ClCCCl.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([CH2:18][N:30]4[CH2:31][CH:32]([N:34]5[CH2:39][CH2:38][NH:37][C:36](=[O:40])[CH2:35]5)[CH2:33]4)[N:14]3[CH3:17])=[C:10]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)[N:9]=2)[C:6]2[CH:26]=[CH:27][CH:28]=[CH:29][C:5]=2[N:4]=1)[CH3:2]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 5049666Sodium triacetoxyborohydrideHCID 596059872-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehydeHCID 596061454-(Azetidin-3-yl)piperazin-2-one

Product 1

HCID 596055114-(1-((2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)azetidin-3-yl)piperazin-2-one

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (100 mg, 0.26 mmol), 4-azetidin-3-ylpiperazin-2-one (44 mg, 0.28 mmol) and 4 Å powdered molecular sieves (250 mg) in MeOH (2 mL) and DCE (5 mL) was stirred at room temperature for 2 h before the addition of sodium triacetoxyborohydride (108 mg, 0.51 mmol). The reaction mixture was stirred for 16 h then filtered through celite, washing with DCM. The organic phase was washed with brine (×1) and concentrated in vacuo. The organic phase was dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-7%). The resulting oil was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH/DCM and the product eluted with 2M NH3/MeOH affording 514 as a yellow foam (42 mg, 31%). LCMS (Method I): RT 2.28 min [M+H]+ 531.2. 1H NMR (CDCl3, 400 MHz): δ 8.02-7.97 (m, 1 H); 7.79-7.74 (m, 1 H); 7.31-7.24 (m, 2 H); 5.93 (bs, 1 H); 4.35 (m, 4 H); 3.94 (s, 2 H); 3.94-3.80 (m, 7 H); 3.66 (bs, 2 H); 3.43-3.33 (m, 4 H); 3.21 (s, 3 H); 3.06 (s, 2 H); 2.58 (t, J=5.37 Hz, 2 H) and 1.45 (t, J=7.5 Hz, 3 H)

Workup

  1. filtrationthen filtered through celite
  2. washwashing with DCM
  3. washThe organic phase was washed with brine (×1)
  4. concentrationconcentrated in vacuo
  5. dry with materialThe organic phase was dried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-7%)
  8. washwas washed with MeOH/DCM
  9. washthe product eluted with 2M NH3/MeOH affording 514 as a yellow foam (42 mg, 31%)
  10. customRT 2.28 min [M+H]+ 531.2

Sources & evidence

ORD record
ord-7ed3af7632074cb39eabb81958318927
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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