Diisopropylethylamine → HCID 178516973, compound

HRID 707443Notes

Reaction equation

HRID 707443 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([N:8]2[C:12]3=[N:13][CH:14]=[CH:15][N:16]=[C:11]3[N:10]([CH:17]3[CH2:19][CH2:18]3)[C:9]2=[O:20])[CH2:4][CH2:3]1.Cl[C:22]1[CH:31]=[CH:30][C:29]2[C:24](=[CH:25][CH:26]=[CH:27][N:28]=2)[N:23]=1.C(N(C(C)C)CC)(C)C>CS(C)=O>[N:23]1[C:24]2[C:29](=[N:28][CH:27]=[CH:26][CH:25]=2)[CH:30]=[CH:31][C:22]=1[NH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([N:8]2[C:12]3=[N:13][CH:14]=[CH:15][N:16]=[C:11]3[N:10]([CH:17]3[CH2:19][CH2:18]3)[C:9]2=[O:20])[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 151530312-Chloro-1,5-naphthyridineHCID 178511583HCID 178511583, compound

Product 1

HCID 178516973HCID 178516973, compoundYield 4.7%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

A glass microwave reaction vessel was charged with 1-(trans-4-aminocyclohexyl)-3-cyclopropyl-1H-imidazo[4,5-b]pyrazin-2(3H)-one (0.1050 g, 0.339 mmol), 2-chloro-1,5-naphthyridine (0.067 g, 0.407 mmol, 00358), and diisopropylethylamine (0.177 ml, 1.017 mmol, Sigma-Aldrich Chemical Company, Inc.) in DMSO (0.484 ml) and heated to 120° C. for 2 days. The crude product was purified by reverse-phase preparative HPLC using a Phenomenex Gemini column, 10 micron, 100×50 mm, 0.1% TFA in CH3CN/H2O, gradient 10% to 90% over 15 min. Fractions containing product were collected and concentrated. The product was taken up in DCM and loaded onto a Silicycle Si-carbonate cartridge and washed with DCM and MeOH to remove any salts to give the title compound (6.4 mg, 0.016 mmol, 4.7% yield). LCMS showed product peak at 1.434 min (m+1=402.0). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.09-1.24 (m, 4 H) 1.37-1.53 (m, 2 H) 1.94 (d, J=11.93 Hz, 2 H) 2.39 (d, J=12.13 Hz, 2 H) 2.68 (qd, J=12.91, 3.13 Hz, 2 H) 2.97-3.09 (m, 1 H) 4.08-4.24 (m, 1 H) 4.47 (tt, J=12.32, 3.91 Hz, 1 H) 6.85 (d, J=9.19 Hz, 1 H) 7.45 (dd, J=8.41, 4.30 Hz, 1 H) 7.91-7.96 (m, 2 H) 7.97 (d, J=8.61 Hz, 1 H) 8.03 (d, J=9.19 Hz, 1 H) 8.60 (d, J=3.33 Hz, 1 H)

Workup

  1. customA glass microwave reaction vessel
  2. customThe crude product was purified by reverse-phase preparative HPLC
  3. customover 15 min
  4. additionFractions containing product
  5. customwere collected
  6. concentrationconcentrated
  7. washwashed with DCM and MeOH
  8. customto remove any salts

Sources & evidence

ORD record
ord-63e92869be6841f8a82c50e633ad426c
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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