Diisopropylamine → HCID 178516976, compound

HRID 707435Notes

Reaction equation

HRID 707435 reaction equation
Cl.[NH2:2][C@H:3]1[CH2:6][C@H:5]([N:7]2[C:11]3=[N:12][CH:13]=[CH:14][N:15]=[C:10]3[N:9]([CH:16]3[CH2:18][CH2:17]3)[C:8]2=[O:19])[CH2:4]1.Cl[C:21]1[O:22][C:23]2[CH:29]=[CH:28][CH:27]=[CH:26][C:24]=2[N:25]=1.C(NC(C)C)(C)C>CS(C)=O>[O:22]1[C:23]2[CH:29]=[CH:28][CH:27]=[CH:26][C:24]=2[N:25]=[C:21]1[NH:2][C@H:3]1[CH2:6][C@H:5]([N:7]2[C:11]3=[N:12][CH:13]=[CH:14][N:15]=[C:10]3[N:9]([CH:16]3[CH2:17][CH2:18]3)[C:8]2=[O:19])[CH2:4]1

Participants

5

Reactant 3

HCID 7912DiisopropylamineHCID 119862-ChlorobenzoxazoleHCID 178479284HCID 178479284, compound2×

Product 1

HCID 178516976HCID 178516976, compoundYield 42.4%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A glass microwave reaction vessel was charged with 1-(trans-3-aminocyclobutyl)-3-cyclopropyl-1H-imidazo[4,5-b]pyrazin-2(3H)-one hydrochloride (Intermediate 79, 0.1099 g, 0.390 mmol), 2-chlorobenzoxazole (0.088 ml, 0.768 mmol, Sigma-Aldrich Chemical Company, Inc.), and diisopropylamine (0.204 ml, 1.170 mmol, Sigma-Aldrich Chemical Company, Inc.) in DMSO. The reaction was heated to 90° C. for 24 h The crude product was purified by reverse-phase preparative HPLC using a Phenomenex Gemini column, 10 micron, C18, 110 Å, 100×50 mm, 0.1% TFA in CH3CN/H2O, gradient 10% to 909% over 15 min. LCMS showed product was not isolated at ≧95% purity. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage SNAP HP-silica gel column (25 g), eluting with a gradient of % to 5% MeOH in CH2Cl2, to provide the title compound (0.0590 g, 0.163 mmol, 42.4% yield). LCMS showed product peak at 1.604 min (m+1=362.9). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.96-1.02 (m, 2 H) 1.02-1.09 (m, 2 H) 2.52-2.58 (m, 1 H) 2.91-3.01 (m, 1 H) 3.18-3.30 (m, 2 H) 4.46-4.59 (m, 1 H) 5.11-5.23 (m, 1 H) 6.99 (td, J=7.73, 1.37 Hz, 1 H) 7.12 (td, J=7.63, 1.17 Hz, 1 H) 7.27 (dd, J=7.73, 0.68 Hz, 1 H) 7.36 (dd, J=7.82, 0.59 Hz, 1 H) 7.94-7.98 (m, 1 H) 7.99-8.02 (m, 1 H) 8.42 (d, J=6.46 Hz, 1 H)

Workup

  1. customA glass microwave reaction vessel
  2. customwas purified by reverse-phase preparative HPLC
  3. customover 15 min
  4. customwas not isolated at ≧95% purity
  5. customchromatographed through a Biotage SNAP HP-silica gel column (25 g)
  6. washeluting with a gradient of % to 5% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-a384b532ccb947db92a6ba8414243576
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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