Diisopropylethylamine → HCID 178481624, compound

HRID 707411Notes

Reaction equation

HRID 707411 reaction equation
Cl.[NH2:2][C@H:3]1[CH2:6][C@H:5]([N:7]2[C:11]3=[N:12][CH:13]=[C:14]([F:16])[CH:15]=[C:10]3[N:9]([CH3:17])[C:8]2=[O:18])[CH2:4]1.Cl[C:20]1[S:21][C:22]2[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:23]=2[N:24]=1.C(N(CC)C(C)C)(C)C>CS(C)=O.O>[F:16][C:14]1[CH:15]=[C:10]2[N:9]([CH3:17])[C:8](=[O:18])[N:7]([C@H:5]3[CH2:6][C@H:3]([NH:2][C:20]4[S:21][C:22]5[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:23]=5[N:24]=4)[CH2:4]3)[C:11]2=[N:12][CH:13]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 20498702-Chloro-6-fluorobenzothiazoleHCID 178478930HCID 178478930, compound

Product 1

HCID 178481624HCID 178481624, compoundYield 43.6%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

3-(trans-3-aminocyclobutyl)-6-fluoro-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one hydrochloride (0.100 g, 0.367 mmol), 2-chloro-6-fluorobenzothiazole (0.083 g, 0.440 mmol), and N,N-diisopropylethylamine (0.255 mL, 1.467 mmol) were mixed in DMSO (0.5 mL) in a sealed tube. The reaction mixture was stirred at 120° C. for 5 h. The reaction mixture was cooled to room temperature, diluted with water, and extracted with EtOAc. The organic layer was separated, washed with saturated aqueous sodium chloride, dried over magnesium sulfate, filtered, and concentrated. The resulting crude product was purified by silica gel column chromatography eluting with EtOAc in hexanes to yield the title compound (0.062 g, 0.160 mmol, 43.6% yield) as an off-white solid. M+1: 388.1. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.40-2.49 (m, 2 H) 3.25-3.34 (m, 2 H) 3.36 (s, 3 H) 4.50-4.59 (m, 1 H) 5.21 (quin, J=8.36 Hz, 1 H) 7.08 (td, J=9.10, 2.74 Hz, 1 H) 7.41 (dd, J=8.80, 4.89 Hz, 1 H) 7.62-7.71 (m, 2 H) 8.05 (t, J=2.25 Hz, 1 H) 8.57 (d, J=6.26 Hz, 1 H).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with EtOAc
  3. customThe organic layer was separated
  4. washwashed with saturated aqueous sodium chloride
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting crude product was purified by silica gel column chromatography
  9. washeluting with EtOAc in hexanes

Sources & evidence

ORD record
ord-8f1328bc981f4dc5894010076544cbb2
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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