Methanol → 4-((2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)-1-isopropylpiperazin-2-one

HRID 1945991Notes

Reaction equation

HRID 1945991 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].[CH:30]([N:33]1[CH2:38][CH2:37][NH:36][CH2:35][C:34]1=[O:39])([CH3:32])[CH3:31].CO.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([CH2:18][N:36]4[CH2:37][CH2:38][N:33]([CH:30]([CH3:32])[CH3:31])[C:34](=[O:39])[CH2:35]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 887MethanolHCID 5049666Sodium triacetoxyborohydrideHCID 150574011-(Propan-2-yl)piperazin-2-oneHCID 596059872-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde

Product 1

HCID 596060534-((2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)-1-isopropylpiperazin-2-oneYield 22%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of 2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (0.15 g, 0.39 mmol), 1-isopropylpiperazin-2-one (0.082 g, 0.58 mmol) and 4 Å molecular sieves (0.718 g) in DCE (5 mL) and MeOH (1 mL) was stirred for 5 h at room temperature. Sodium triacetoxyborohydride (0.163 g, 0.77 mmol) was added and the reaction mixture was stirred for 72 h at room temperature. The reaction mixture was filtered through Celite and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography (Si—PPC, MeOH:EtOAc, gradient 0:100 to 5:95) followed by reverse phase HPLC (Phenomenex Gemini 5u C18, 20 mM triethylamine in water on a gradient of acetonitrile 95:5 to 2:98) to give 469 as an off-white solid (0.044 g, 22%). LCMS (Method I): RT=3.31 min, [M+H]+ 518.3. 1H NMR (400 MHz, DMSO-d6): δ 8.04-8.00 (m, 1 H); 7.65-7.61 (m, 1 H); 7.28-7.21 (m, 2 H); 4.64-4.58 (m, 1 H); 4.28-4.25 (m, 4 H); 3.86 (s, 2 H); 3.81 (s, 3 H); 3.80-3.77 (m, 4 H); 3.27 (q, 7.5 Hz, 2 H); 3.17 (t, J=5.3 Hz, 2 H); 3.13 (s, 2 H); 2.73 (t, J=5.3 Hz, 2 H); 1.34 (t, J=7.5 Hz, 3 H); 1.05 (d, J=6.8 Hz, 6 H)

Workup

  1. filtrationThe reaction mixture was filtered through Celite
  2. concentrationthe filtrate was concentrated in vacuo
  3. customThe residue was purified by flash chromatography (Si—PPC, MeOH:EtOAc, gradient 0:100 to 5:95)

Sources & evidence

ORD record
ord-011fd3f6531747b8a3a8265ee27ba027
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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