Triethylamine → (1-(cyclopropanecarbonyl)piperidin-4-yl)(2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methanone

HRID 1946203Notes

Reaction equation

HRID 1946203 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.[CH:43]1([C:46](Cl)=[O:47])[CH2:45][CH2:44]1>C(Cl)Cl>[CH:43]1([C:46]([N:23]2[CH2:22][CH2:21][CH:20]([C:18]([C:13]3[N:14]([CH3:17])[C:15]4[C:11]([N:12]=3)=[C:10]([N:26]3[CH2:27][CH2:28][O:29][CH2:30][CH2:31]3)[N:9]=[C:8]([N:7]3[C:6]5[CH:32]=[CH:33][CH:34]=[CH:35][C:5]=5[N:4]=[C:3]3[CH2:1][CH3:2])[N:16]=4)=[O:19])[CH2:25][CH2:24]2)=[O:47])[CH2:45][CH2:44]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 77637Cyclopropanecarbonyl chlorideHCID 59605539[2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]piperidin-4-ylmethanone

Product 1

HCID 59606030(1-(cyclopropanecarbonyl)piperidin-4-yl)(2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methanoneYield 25%

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 (47 mg, 0.10 mmol) and NEt3 (27 μL, 0.20 mmol) in DCM (5 mL) was added cyclopropane carbonyl 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 30-70%) affording 864 (13 mg, 25%). LCMS (method I): RT 4.06 min, [M+H]+ 543.3. 1H NMR (CDCl3, 400 MHz): δ 8.07-8.06 (1 H, m), 7.89-7.82 (1 H, m), 7.40-7.30 (2 H, m), 4.70-4.56 (3 H, m), 4.39-4.28 (1 H, m), 4.13 (3 H, s), 3.93-3.90 (6 H, m), 3.52-3.27 (3 H, m), 2.94-2.80 (1 H, m), 2.08-1.97 (2 H, m), 1.97-1.57 (4 H, m), 1.50 (3 H, t, J=7.40 Hz), 1.04-0.98 (2 H, m), 0.79-0.78 (2 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 30-70%)

Sources & evidence

ORD record
ord-798d4b6f27ec4582a0871596427a752c
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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