Acetone → 3-(2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)-1-isopropylazetidin-3-ol

HRID 1923331Notes

Reaction equation

HRID 1923331 reaction equation
[CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([C:18]4([OH:22])[CH2:21][NH:20][CH2:19]4)[N:14]3[CH3:17])=[C:10]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[N:9]=2)[C:6]2[CH:29]=[CH:30][CH:31]=[CH:32][C:5]=2[N:4]=1)[CH3:2].[CH3:33][C:34](=O)[CH3:35].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]([C:18]4([OH:22])[CH2:21][N:20]([CH:34]([CH3:35])[CH3:33])[CH2:19]4)[N:14]3[CH3:17])=[C:10]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[N:9]=2)[C:6]2[CH:29]=[CH:30][CH:31]=[CH:32][C:5]=2[N:4]=1)[CH3:2]

Participants

5

Reactant 3

HCID 180AcetoneHCID 5049666Sodium triacetoxyborohydrideHCID 596060743-[2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]azetidine-3-ol

Product 1

HCID 596061173-(2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)-1-isopropylazetidin-3-olYield 13.7%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of 3-[2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]-azetidin-3-ol (100 mg, 0.23 mmol), propan-2-one (34 μL, 27 mg, 0.46 mmol) and 4 Å powdered molecular sieves (150 mg) in DCE (3 mL) was stirred for 3 h before sodium triacetoxyborohydride (96 mg, 0.46 mmol) was added. The resulting mixture was stirred for 16 h at r.t., then filtered through Celite®, washing with DCM. The filtrate was washed with brine, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, MeOH:EtOAc, 0-20%) followed by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 20 mM triethylamine in water on a gradient of acetonitrile 50-70%) affording 738 as a white solid (15 mg, 13%). LCMS (method I): RT 2.43 min, [M+H]+ 477.2. 1H NMR (MeOD, 400 MHz): δ 8.01-8.01 (1 H, m), 7.64-7.61 (1 H, m), 7.29-7.28 (2 H, m), 4.39 (5 H, s), 4.19-4.17 (2 H, m), 3.85 (4 H, s), 3.46 (2 H, d, J=8.87 Hz), 3.31-3.30 (5 H, m), 2.56-2.54 (1 H, m), 1.39 (3 H, t, J=7.50 Hz), 1.01 (6 H, d, J=6.25 Hz)

Workup

  1. additionwas added
  2. filtrationfiltered through Celite®
  3. washwashing with DCM
  4. washThe filtrate was washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by column chromatography (Si-PCC, MeOH:EtOAc, 0-20%)

Sources & evidence

ORD record
ord-1039cf590aed46d4bfde52996746e0a7
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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