Triethylamine → HCID 59605476, compound

HRID 1946193Notes

Reaction equation

HRID 1946193 reaction equation
[CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([CH2:18][CH:19]4[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]4)[N:14]3[CH3:17])=[C:10]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[N:9]=2)[C:6]2[CH:31]=[CH:32][CH:33]=[CH:34][C:5]=2[N:4]=1)[CH3:2].[CH:35]1([C:38](Cl)=[O:39])[CH2:37][CH2:36]1.CCN(CC)CC>C(Cl)Cl>[CH:35]1([C:38]([N:22]2[CH2:21][CH2:20][CH:19]([CH2:18][C:13]3[N:14]([CH3:17])[C:15]4[C:11]([N:12]=3)=[C:10]([N:25]3[CH2:26][CH2:27][O:28][CH2:29][CH2:30]3)[N:9]=[C:8]([N:7]3[C:6]5[CH:31]=[CH:32][CH:33]=[CH:34][C:5]=5[N:4]=[C:3]3[CH2:1][CH3:2])[N:16]=4)[CH2:24][CH2:23]2)=[O:39])[CH2:37][CH2:36]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 77637Cyclopropanecarbonyl chlorideHCID 674926242-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-8-piperidin-4-ylmethyl-9H-purine

Product 1

HCID 59605476HCID 59605476, compoundYield 17.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-8-piperidin-4-ylmethyl-9H-purine (230 mg, 0.50 mmol), cyclopropyl carbonyl chloride (50 μL, 0.55 mmol) and NEt3 (140 μL, 1.00 mmol) in DCM (10 mL) was allowed to stir at r.t. for 5 h then concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-5%) then further purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 20 mM triethylamine in water on a gradient of acetonitrile 40-98%) affording 852 as a white solid (46 mg, 17%). LCMS (method I): RT 3.59 min, [M+H]+ 529.4. 1H NMR (DMSO, 400 MHz): δ 8.03-7.99 (1 H, m), 7.64-7.63 (1 H, m), 7.25-7.24 (2 H, m), 4.45-4.10 (6 H, m), 3.77-3.75 (6 H, m), 3.27-3.24 (3 H, m), 3.16-3.00 (1 H, m), 2.86 (2 H, d, J=7.07 Hz), 2.64-2.47 (1 H, m), 2.20-2.08 (1 H, m), 2.01-1.93 (1 H, m), 1.79-1.71 (2 H, m), 1.33 (3 H, t, J=7.43 Hz), 1.30-1.07 (2 H, m), 0.74-0.66 (4 H, m)

Workup

  1. concentrationthen concentrated in vacuo
  2. customThe resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-5%)
  3. customthen further purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 20 mM triethylamine in water on a gradient of acetonitrile 40-98%)

Sources & evidence

ORD record
ord-b35939e5d1744f4b8d496e0b0265ee38
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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