Sodium triacetoxyborohydride → 4-(8-((2,2-dimethyl-4-(methylsulfonyl)piperazin-1-yl)methyl)-2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-9H-purin-6-yl)morpholine

HRID 1946102

Reaction equation

HRID 1946102 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].[CH3:30][S:31]([N:34]1[CH2:39][CH2:38][NH:37][C:36]([CH3:41])([CH3:40])[CH2:35]1)(=[O:33])=[O:32].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH3:40][C:36]1([CH3:41])[CH2:35][N:34]([S:31]([CH3:30])(=[O:33])=[O:32])[CH2:39][CH2:38][N:37]1[CH2:18][C:13]1[N:14]([CH3:17])[C:15]2[C:11]([N:12]=1)=[C:10]([N:20]1[CH2:21][CH2:22][O:23][CH2:24][CH2:25]1)[N:9]=[C:8]([N:7]1[C:6]3[CH:26]=[CH:27][CH:28]=[CH:29][C:5]=3[N:4]=[C:3]1[CH2:1][CH3:2])[N:16]=2

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 198151421-Methanesulfonyl-3,3-dimethylpiperazineHCID 596059872-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde

Product 1

HCID 596054304-(8-((2,2-dimethyl-4-(methylsulfonyl)piperazin-1-yl)methyl)-2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-9H-purin-6-yl)morpholineYield 13%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of 2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (167 mg, 0.43 mmol), 1-methanesulfonyl-3,3-dimethylpiperazine (100 mg, 0.52 mmol) and molecular sieves (4 Å, powdered, 830 mg) in DCE (10 mL) was stirred at ambient temperature for 5 h. Sodium triacetoxyborohydride (136 mg, 0.64 mmol) was added and the mixture stirred for 17 h, then loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was then washed with methanol and the desired product was subsequently eluted using 2 M NH3 in MeOH. The product was collected and concentrated in vacuo. The resultant residue was purified by flash chromatography (Si—PPC, DCM:MeOH, 100:0 to 99:1 to 98:2 to 95:5) followed by reverse phase HPLC (Phenomenex Gemini 5u C18, 20 mM triethylamine in water on a gradient of acetonitrile 51:49 to 49:51) to afford 596 as a cream foam (31 mg, 13%). LCMS (method I): RT=3.42 min, M+H+=568. 1H NMR (CDCl3, 400 MHz) δ 8.01 (m, 1 H), 7.77 (m, 1 H), 7.26 (m, 2 H), 4.34 (m, 4 H), 3.87 (m, 9 H), 3.36 (q, J=7.5 Hz, 2 H), 3.16 (m, 2 H), 3.02 (s, 2 H), 2.77 (s, 3 H), 2.64 (m, 2 H), 1.46 (t, J=7.5 Hz, 3 H) and 1.29 (s, 6 H)

Workup

  1. washThe cartridge was then washed with methanol
  2. washthe desired product was subsequently eluted
  3. customThe product was collected
  4. concentrationconcentrated in vacuo
  5. customThe resultant residue was purified by flash chromatography (Si—PPC, DCM:MeOH, 100:0 to 99:1 to 98:2 to 95:5)

Sources & evidence

ORD record
ord-93d81819185a4d508aa8195342f26c28
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Linked notes

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