Acetic Acid → 2-(2-Ethyl-1H-benzimidazol-1-yl)-9-methyl-6-(4-morpholinyl)-8-[[3-(tetrahydro-2H-pyran-4-yl)-1-azetidinyl]methyl]-9H-purine

HRID 1923070Notes

Reaction equation

HRID 1923070 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].[O:30]1[CH2:35][CH2:34][CH:33]([CH:36]2[CH2:39][NH:38][CH2:37]2)[CH2:32][CH2:31]1.COC(OC)OC.C(O)(=O)C.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:38]4[CH2:39][CH:36]([CH:33]5[CH2:34][CH2:35][O:30][CH2:31][CH2:32]5)[CH2:37]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

7

Reactant 5

HCID 176Acetic AcidHCID 9005Trimethyl orthoformateHCID 5049666Sodium triacetoxyborohydrideHCID 177856443-(Oxan-4-yl)azetidineHCID 596059872-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde

Product 1

HCID 596061382-(2-Ethyl-1H-benzimidazol-1-yl)-9-methyl-6-(4-morpholinyl)-8-[[3-(tetrahydro-2H-pyran-4-yl)-1-azetidinyl]methyl]-9H-purineYield 56%

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 (0.10 g, 0.26 mmol), 3-(tetrahydropyran-4-yl)azetidine (0.050 g, 0.28 mmol) in DCE (2 mL), trimethoxymethane (0.277 mL, 2.6 mmol) and acetic acid (0.015 mL, 0.26 mmol) was stirred for 2 h at room temperature. Sodium triacetoxyborohydride (0.090 g, 0.43 mmol) was added and the reaction mixture was stirred for 18 h at room temperature. The reaction mixture was partitioned between DCM and water, the organic phase was separated, washed with brine, dried over sodium sulphate and concentrated. The residue was purified by flash chromatography (Si—PPC, MeOH:EtOAc gradient 0:100 to 10:90) to give 325 as a yellow solid (0.072 g, 56%). LCMS (Method G): RT=6.14 min, [M+H]+ 517.2. 1H NMR (CDCl3, 400 MHz) δ 8.02-7.98 (m, 1 H); 7.78-7.73 (m, 1 H); 7.35-7.25 (m, 2 H); 4.40-4.32 (m, 4 H); 3.98 (dd, J=11.7, 4.3 Hz, 2 H); 3.89-3.86 (m, 9 H); 3.42-3.30 (m, 5 H); 1.67-1.64 (m, 4 H); 1.55 (d, J=11.7 Hz, 2 H); 1.48-1.39 (t, J=7.5 Hz, 3 H); 1.29-1.16 (m, 3 H)

Workup

  1. stirringthe reaction mixture was stirred for 18 h at room temperature
  2. customThe reaction mixture was partitioned between DCM and water
  3. customthe organic phase was separated
  4. washwashed with brine
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography (Si—PPC, MeOH:EtOAc gradient 0:100 to 10:90)

Sources & evidence

ORD record
ord-cbfb6c2757b54c05996d3c8f3935ab16
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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