2-Chloroquinazoline → HCID 178481626, compound

HRID 707404Notes

Reaction equation

HRID 707404 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[N:29]=[CH:28][C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:21]=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[N:29]=[CH:28][C:27]5[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=5)[N:21]=4)[CH2:4]3)[C:11]2=[N:12][CH:13]=1

Participants

6

Reactant 3

HCID 740542-ChloroquinazolineHCID 81531DiisopropylethylamineHCID 178478930HCID 178478930, compound

Product 1

HCID 178481626HCID 178481626, compoundYield 38.5%

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 (0.105 g, 0.385 mmol), 2-chloroquinazoline (0.076 g, 0.462 mmol), and N,N-diisopropylethylamine (0.268 mL, 1.540 mmol) were mixed in DMSO (0.5 mL). The reaction mixture was warmed to 120° C. and stirred for 3 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 in vacuo. The resulting crude product was purified by silica gel column chromatography eluting with EtOAc in hexanes to yield 6-fluoro-1-methyl-3-(trans-3-(quinazolin-2-ylamino)cyclobutyl)-1H-imidazo[4,5-b]pyridin-2(3h)-one (0.054 g, 0.148 mmol, 38.5% yield) as a yellow solid. M+1: 365.1. 1H NMR (400 MHz, DMSO-d) δ ppm 2.42-2.50 (m, 2 H) 3.25-3.34 (m, 2 H) 3.35 (s, 3 H) 4.63-4.74 (m, 1 H) 5.25 (quin, J=8.51 Hz, 1 H) 7.22-7.27 (m, 1 H) 7.49 (d, J=8.41 Hz, 1 H) 7.64-7.73 (m, 2 H) 7.81 (dd, J=8.02, 0.78 Hz, 1 H) 7.99 (br. d, J=6.30 Hz, 1 H) 8.05 (t, J=2.25 Hz, 1 H) 9.15 (s, 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 in vacuo
  8. customThe resulting crude product was purified by silica gel column chromatography
  9. washeluting with EtOAc in hexanes

Sources & evidence

ORD record
ord-6fc1458e78bc446a9bbddde7485a19c1
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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