2-Chlorobenzothiazole → HCID 178517871, compound

HRID 707415Notes

Reaction equation

HRID 707415 reaction equation
Br.[NH2:2][C@H:3]1[CH2:6][C@H:5]([N:7]2[C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[C:9]([F:17])([F:16])[C:8]2=[O:18])[CH2:4]1.Cl[C:20]1[S:21][C:22]2[CH:28]=[CH:27][CH:26]=[CH:25][C:23]=2[N:24]=1.C(N(CC)C(C)C)(C)C>CS(C)=O.O>[S:21]1[C:22]2[CH:28]=[CH:27][CH:26]=[CH:25][C:23]=2[N:24]=[C:20]1[NH:2][C@H:3]1[CH2:6][C@H:5]([N:7]2[C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[C:9]([F:17])([F:16])[C:8]2=[O:18])[CH2:4]1

Participants

6

Reactant 3

HCID 119872-ChlorobenzothiazoleHCID 81531DiisopropylethylamineHCID 178419706HCID 178419706, compound

Product 1

HCID 178517871HCID 178517871, compoundYield 30.7%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

1-(Trans-3-aminocyclobutyl)-3,3-difluoro-1H-pyrrolo[2,3-b]pyridin-2(3H)-one hydrobromide (0.084 g, 0.262 mmol), 2-chlorobenzothiazole (0.0534 g, 0.315 mmol), and N,N-diisopropylethylamine (0.183 mL, 1.050 mmol) were mixed in DMSO (0.5 mL) in a sealed tube. The reaction mixture was stirred at 120° C. for 2 hr. 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 the title compound (0.030 g, 0.081, 30.7% yield) as a white solid. M+1: 373.1. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.39-2.49 (m, 2 H) 3.19-3.30 (m, 2 H) 4.48-4.58 (m, 1 H) 5.10 (quin, J=8.36 Hz, 1 H) 7.04 (t, J=7.53 Hz, 1 H) 7.21-7.26 (m, 1 H) 7.29 (dd, J=7.34, 5.38 Hz, 1 H) 7.43 (d, J=7.82 Hz, 1 H) 7.70 (d, J=7.24 Hz, 1 H) 8.20 (dd, J=7.43, 1.37 Hz, 1 H) 8.51-8.56 (m, 2 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-792f9900e8ae4fbcbdaa0095f676bff1
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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