Water → HCID 57584984, compound

HRID 2077594Notes

Reaction equation

HRID 2077594 reaction equation
O.C(=O)([O-])[O-].[Na+].[Na+].O.CC1(C)C(C)(C)OB([C:17]2[CH:29]=[CH:28][C:20]3[N:21]=[C:22]([NH:24][C:25](=[O:27])[CH3:26])[S:23][C:19]=3[CH:18]=2)O1.Br[C:32]1[CH:33]=[C:34]([O:38][CH2:39][CH2:40][NH:41][C:42](=[O:46])[CH2:43][O:44][CH3:45])[CH:35]=[N:36][CH:37]=1>[Pd].C1COCC1>[C:25]([NH:24][C:22]1[S:23][C:19]2[CH:18]=[C:17]([C:32]3[CH:33]=[C:34]([O:38][CH2:39][CH2:40][NH:41][C:42](=[O:46])[CH2:43][O:44][CH3:45])[CH:35]=[N:36][CH:37]=3)[CH:29]=[CH:28][C:20]=2[N:21]=1)(=[O:27])[CH3:26]

Participants

7

Reactant 4

HCID 962WaterHCID 2735133Sodium Carbonate MonohydrateHCID 51354026n-(6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazol-2-yl)acetamideHCID 67097795Acetamide, N-[2-[(5-bromo-3-pyridinyl)oxy]ethyl]-2-methoxy-

Product 1

HCID 57584984HCID 57584984, compoundYield 26%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst2×HCID 8028TetrahydrofuranSolvent2×

Procedure

A Biotage high recovery microwave vessel was charged with sodium carbonate hydrate (0.048 g, 0.38 mmol), 0.15 mL water and a stirbar. The slurry was sonicated and stirred for 10 minutes. An inert atmosphere inlet was placed over the vessel and the remaining reagents were added under a flow of nitrogen. To the vessel was added N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazol-2-yl)acetamide (0.043 g, 0.14 mmol), 100 mg Pd FibreCat® palladium catalyst, and N-(2-(5-bromopyridin-3-yloxy)ethyl)-2-methoxyacetamide (0.0247 g, 0.085 mmol) dissolved in 1 mL THF. The vessel was sealed, and irritated using a Biotage personal chemistry microwave reactor to 130° C. for 25 minutes. The cooled reaction was diluted with 5 mL THF, and filtered through a 0.22 μm PTFE membrane. The catalyst was washed with THF (2×5 mL), and the combined filtrates were concentrated in vacuo. The residue was sonicated in 2 mL water, and filtered. The precipitate was then dissolved in 3 mL MeOH, filtered, and concentrated in vacuo. The crude was purified using a 19×150 mm Waters Xterra Prep C18 OBD column (100 Å pore diameter, 5 μm particle size, spherical shape, PN 186002381; Gradient: 0→5 min@20 mL/min, 10% B; 5.0→35 min@20 mL/min, linear gradient to 40% B; 35→45@20 mL/min, isocratic at 40% B, 45→55 min@20 mL/min, step to 100% B; 55→60 min@20 mL/min, step to 10% B; 60 min end; A=10.7 mM NH4HCO3 in water, pH adjusted to 8.6 with concentrated NH4OH; B acetonitrile). A band that eluted from 24.2 to 26.0 minutes was isolated. The solvent was removed in vacuo to afford N-(2-(5-(2-(N-actyl)aminobenzo[d]thiazol-6-yl)pyridin-3-yloxy)ethyl)-2-methoxyacetamide. (0.0090 g, 26% yield). 1H NMR (400 MHz, DMF) δ ppm 2.34 (s, 3H) 3.37 (s, 3H) 3.70 (q, J=5.84 Hz, 2H) 3.89 (s, 2H) 4.35 (t, J=5.97 Hz, 2H) 7.81 (dd, J=2.54, 1.96 Hz, 1H) 7.83 (s, 1H) 7.85 (s, 1H) 7.86-7.90 (m, J=8.41, 1.86 Hz, 1H) 8.32 (d, J=2.25 Hz, 1H) 8.47 (d, J=1.47 Hz, 1H) 8.62 (br. s., 1H) 12.35 (br. s., 1H). 13C NMR (101 MHz, DMF) δ ppm 22.46 (s, 1 C) 38.02 (s, 1 C) 58.54 (s, 1 C) 66.92 (s, 1 C) 71.91 (s, 1 C) 118.91 (s, 1 C) 120.35 (s, 1 C) 121.07 (s, 1 C) 125.49 (s, 1 C) 132.82 (s, 1 C) 133.22 (s, 1 C) 136.79 (s, 1 C) 137.04 (s, 1 C) 140.37 (s, 1 C) 149.26 (s, 1 C) 155.35 (s, 1 C) 159.21 (s, 1 C) 169.69 (s, 1 C) 169.72 (s, 1 C). HPLC-MS: retention time=1.12 min (99.3%@215 nm; 98.1% @254 nm; m/z=401.1, calculated for C19H20N4O4S+H+=401.1).

Workup

  1. customThe slurry was sonicated
  2. customAn inert atmosphere inlet was placed over the vessel
  3. additionthe remaining reagents were added under a flow of nitrogen
  4. customThe vessel was sealed
  5. customto 130° C.
  6. customfor 25 minutes
  7. customThe cooled reaction
  8. filtrationfiltered through a 0.22 μm PTFE membrane
  9. washThe catalyst was washed with THF (2×5 mL)
  10. concentrationthe combined filtrates were concentrated in vacuo
  11. customThe residue was sonicated in 2 mL water
  12. filtrationfiltered
  13. dissolutionThe precipitate was then dissolved in 3 mL MeOH
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo
  16. customThe crude was purified
  17. custom0→5 min@20 mL/min, 10% B
  18. custom5.0→35 min@20 mL/min, linear gradient
  19. customisocratic at 40% B, 45→55 min@20 mL/min, step
  20. custom55→60 min@20 mL/min, step
  21. custom60 min end
  22. washA band that eluted from 24.2 to 26.0 minutes
  23. customwas isolated
  24. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-897f6d6711e54c41be8efd510e608d0d
Source dataset
uspto-grants-2011_04
Patent number
US07928140B2

Reaction notes

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