Triethylamine → HCID 59606197, compound

HRID 1946205Notes

Reaction equation

HRID 1946205 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:21]4[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]4)([OH:20])[CH3:19])[N:14]3[CH3:17])=[C:10]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)[N:9]=2)[C:6]2[CH:33]=[CH:34][CH:35]=[CH:36][C:5]=2[N:4]=1)[CH3:2].CCN(CC)CC.[CH:44]1([C:47](Cl)=[O:48])[CH2:46][CH2:45]1>C(Cl)Cl>[CH:44]1([C:47]([N:24]2[CH2:25][CH2:26][CH:21]([C:18]([C:13]3[N:14]([CH3:17])[C:15]4[C:11]([N:12]=3)=[C:10]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)[N:9]=[C:8]([N:7]3[C:6]5[CH:33]=[CH:34][CH:35]=[CH:36][C:5]=5[N:4]=[C:3]3[CH2:1][CH3:2])[N:16]=4)([OH:20])[CH3:19])[CH2:22][CH2:23]2)=[O:48])[CH2:46][CH2:45]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 77637Cyclopropanecarbonyl chlorideHCID 59605562HCID 59605562, compound

Product 1

HCID 59606197HCID 59606197, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 1-[2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]-1-piperidin-4-ylethanol and NEt3 (74 μL, 0.53 mmol) in DCM (5 mL) was cooled to −78° before the addition of cyclopropane carbonyl chloride (18 μL, 0.20 mmol). The resulting mixture was stirred for 15 min then quenched with H2O and extracted with DCM. The combined organics were dried (phase separator) and concentrated in vacuo. The resulting residue was purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 0.1% NH4OH in water on a gradient acetonitrile 10-70%) affording 865 as a white solid (44 mg, 44%). LCMS (method I): RT 3.51 min, [M+H]+ 559.4. 1H NMR (CDCl3, 400 MHz): δ 8.01-8.00 (1 H, m), 7.80 (1 H, d, J=7.13 Hz), 7.33-7.28 (2 H, m), 4.71 (1 H, brd s), 4.32 (4 H, brd s), 3.98 (3 H, s), 3.87 (4 H, t, J=4.69 Hz), 3.40 (2 H, q, J=7.47 Hz), 3.14-2.98 (1 H, m), 2.60-2.43 (1 H, m), 2.20-2.09 (1 H, m), 1.86-1.65 (6 H, m), 1.62-1.36 (3 H, m), 1.47 (3 H, t, J=7.47 Hz), 1.00-0.93 (2 H, m), 0.75-0.74 (2 H, m)

Workup

  1. customthen quenched with H2O
  2. extractionextracted with DCM
  3. customThe combined organics were dried (phase separator)
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 0.1% NH4OH in water on a gradient acetonitrile 10-70%)

Sources & evidence

ORD record
ord-b81cc92bc9d04710995c9cadecb6ed43
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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