Triethylamine → HCID 59605397, compound

HRID 1923391Notes

Reaction equation

HRID 1923391 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]([CH:20]4[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]4)=[O:19])[N:14]3[CH3:17])=[C:10]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)[N:9]=2)[C:6]2[CH:32]=[CH:33][CH:34]=[CH:35][C:5]=2[N:4]=1)[CH3:2].CCN(CC)CC.[C:43](Cl)(=[O:47])[CH:44]([CH3:46])[CH3:45]>C(Cl)Cl>[CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([C:18]([CH:20]4[CH2:21][CH2:22][N:23]([C:43](=[O:47])[CH:44]([CH3:46])[CH3:45])[CH2:24][CH2:25]4)=[O:19])[N:14]3[CH3:17])=[C:10]([N:26]3[CH2:27][CH2:28][O:29][CH2:30][CH2:31]3)[N:9]=2)[C:6]2[CH:32]=[CH:33][CH:34]=[CH:35][C:5]=2[N:4]=1)[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 62325Isobutyryl chlorideHCID 59605539[2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]piperidin-4-ylmethanone

Product 1

HCID 59605397HCID 59605397, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of [2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]piperidin-4-ylmethanone and NEt3 (27 μL, 0.20 mmol) in DCM (5 mL) was added isobutyryl chloride (10 μL, 0.12 mmol) and the resulting mixture stirred at r.t. for 3 h. The reaction mixture was quenched with H2O and extracted with DCM. The combined organic phases were dried (MgSO4) and concentrated in vacuo and the resulting residue loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The resulting residue was purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 0.1% NH4OH in water on a gradient acetonitrile 40-70%) affording 863 (7 mg, 13%). LCMS (method I): RT 4.19 min, [M+H]+ 545.3. 1H NMR (CDCl3, 400 MHz): δ 8.06-8.05 (1 H, m), 7.88-7.81 (1 H, m), 7.39-7.31 (2 H, m), 4.75-4.63 (2 H, m), 4.14-4.02 (5 H, m), 3.93-3.91 (5 H, m), 3.51-3.40 (2 H, m), 3.31-3.40 (1 H, m), 2.84-2.82 (2 H, m), 2.08-1.96 (2 H, m), 1.89-1.62 (4 H, m), 1.49 (3 H, t, J=7.43 Hz), 1.20-1.12 (6 H, m)

Workup

  1. customThe reaction mixture was quenched with H2O
  2. extractionextracted with DCM
  3. dry with materialThe combined organic phases were dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. washwas washed with MeOH
  6. washthe product eluted with 2M NH3/MeOH
  7. customThe resulting residue was purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 0.1% NH4OH in water on a gradient acetonitrile 40-70%)

Sources & evidence

ORD record
ord-3236f19a759040d88b25a84964f0560f
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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