Water → HCID 86628004, compound

HRID 2077619Notes

Reaction equation

HRID 2077619 reaction equation
[S:1]1[C:5]2[CH:6]=[C:7]([B-](F)(F)F)[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.[K+].Br[C:16]1[CH:17]=[C:18]([O:23][CH2:24][O:25][CH2:26][CH2:27][O:28][CH3:29])[C:19]([Cl:22])=[N:20][CH:21]=1.C(N(CC)CC)C.O>CCO>[Cl:22][C:19]1[N:20]=[CH:21][C:16]([C:7]2[CH:8]=[CH:9][C:4]3[N:3]=[CH:2][S:1][C:5]=3[CH:6]=2)=[CH:17][C:18]=1[O:23][CH2:24][O:25][CH2:26][CH2:27][O:28][CH3:29]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 58229473HCID 58229473, compoundHCID 87267539HCID 87267539, compound

Product 1

HCID 86628004HCID 86628004, compoundYield 10.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A 50 mL Schlenk flask was charged with potassium benzo[d]thiazol-6-yltrifluoroborate (0.1929 g, 0.800 mmol), Pd(dppf)C12-DCM adduct (0.0469 g, 0.0641 mmol) and a stirbar. The flask was evacuated to <1 mm Hg and refilled with nitrogen. A degassed solution of 5-bromo-2-chloro-3-((2-methoxyethoxy)methoxy)pyridine (0.1900 g, 0.641 mmol) in 5 mL 1% aqueous EtOH was added, followed by triethylamine (0.262 ml, 1.92 mmol). The flask was fitted with a cold finger, and was heated using a 110° C. oil bath for 12 h. The solution was cooled, and water (10 mL) was added. The mixture was vigorously stirred for 1 h, and poured onto a glass frit. The oily residue was washed with water (2×10 mL), and then dissolved in MeOH (30 mL). The brownish solution was stirred for 30 minutes, and then filtered through a 0.22 μm PTFE membrane. The filtrate was concentrated in vacuo. The sample was purified in one injection using a 30×100 mm Waters Xterra Prep C18 OBD column (A=water; B=2% TFE in ACN; 100 Å pore diameter, 5 μm particle size, spherical shape, PN 186001942; Gradient: 0→5 min@35 mL/min, 40% B; 5→20 min@35 mL/min, linear gradient to 70% B; 20→24.9@35 mL/min, isocratic at 70% B, 25→29.9 min@35 mL/min, step to 100% B; 30→40 min@35 mL/min, step to 40% B; 40 min end). A fraction that eluted from 14.7 to 15.9 minutes was isolated. The solvent was removed in vacuo to afford 6-(6-chloro-5-((2-methoxyethoxy)methoxy)pyridin-3-yl)benzo[d]thiazole (0.0231 g, 10.3% yield). 1H NMR (400 MHz, chloroform-d) δ ppm 3.37 (s, 3H) 3.58-3.61 (m, 2H) 3.91-3.96 (m, 2H) 5.46 (s, 2H) 7.72 (dd, J=8.51, 1.86 Hz, 1H) 7.83 (d, J=2.15 Hz, 1H) 8.15 (dd, J=1.81, 0.44 Hz, 1H) 8.23 (dd, J=8.51, 0.49 Hz, 1H) 8.35 (d, J=2.05 Hz, 1H) 9.06 (br. s., 1H). 13C NMR (101 MHz, chloroform-d) δ ppm 58.97 (s, 1 C) 68.25 (s, 1 C) 71.34 (s, 1 C) 94.14 (s, 1 C) 120.47 (s, 1 C) 122.57 (s, 1 C) 124.10 (s, 1 C) 125.67 (s, 1 C) 134.15 (s, 1 C) 134.78 (s, 1 C) 136.37 (s, 1 C) 140.24 (s, 1 C) 140.68 (s, 1 C) 149.46 (s, 1 C) 153.22 (s, 1 C) 154.95 (br. s., 1 C). HPLC-MS: 2.06 min (>99%@215 nm; 99.2% @254 nm; m/z=351.1, calculated for C16H15ClN2O3S+H+=351.1).

Workup

  1. customThe flask was evacuated to <1 mm Hg
  2. additionrefilled with nitrogen
  3. customThe flask was fitted with a cold finger
  4. temperaturewas heated
  5. customusing a 110° C.
  6. customfor 12 h
  7. temperatureThe solution was cooled
  8. additionpoured onto a glass frit
  9. washThe oily residue was washed with water (2×10 mL)
  10. dissolutiondissolved in MeOH (30 mL)
  11. stirringThe brownish solution was stirred for 30 minutes
  12. filtrationfiltered through a 0.22 μm PTFE membrane
  13. concentrationThe filtrate was concentrated in vacuo
  14. customThe sample was purified in one injection
  15. custom0→5 min@35 mL/min, 40% B
  16. custom5→20 min@35 mL/min, linear gradient
  17. customisocratic at 70% B, 25→29.9 min@35 mL/min, step
  18. custom30→40 min@35 mL/min, step
  19. custom40 min end
  20. washA fraction that eluted from 14.7 to 15.9 minutes
  21. customwas isolated
  22. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-efba932516a049cd8c7258edb37c0e74
Source dataset
uspto-grants-2011_04
Patent number
US07928140B2

Reaction notes

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