Hydrogen Bromide → HCID 16036676, compound

HRID 2234202Notes

Reaction equation

HRID 2234202 reaction equation
Cl.[NH2:2][CH2:3][CH2:4][C:5]1[C:13]2[S:12][C:11](=[O:14])[NH:10][C:9]=2[C:8]([OH:15])=[CH:7][CH:6]=1.[OH-].[Na+].[CH2:18]([N:20]([CH2:44][CH3:45])[CH2:21][CH2:22][N:23]([CH2:41][CH:42]=O)[C:24](=[O:40])[CH2:25][CH2:26][O:27][CH2:28][CH2:29][C:30]1[CH:39]=[CH:38][C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH:31]=1)[CH3:19].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Br>CN1C(=O)CCC1.CO.C(Cl)Cl.C(O)C.O>[CH2:44]([N:20]([CH2:18][CH3:19])[CH2:21][CH2:22][N:23]([CH2:41][CH2:42][NH:2][CH2:3][CH2:4][C:5]1[C:13]2[S:12][C:11](=[O:14])[NH:10][C:9]=2[C:8]([OH:15])=[CH:7][CH:6]=1)[C:24](=[O:40])[CH2:25][CH2:26][O:27][CH2:28][CH2:29][C:30]1[CH:39]=[CH:38][C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH:31]=1)[CH3:45]

Participants

11

Reactant 5

HCID 260Hydrogen BromideHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 602075534-Hydroxy-7-(2-aminoethyl)-1,3-benzothiazol-2(3H)-one hydrochlorideHCID 86625183HCID 86625183, compound

Product 1

HCID 16036676HCID 16036676, compoundYield 34.2%

Reagents, catalysts & solvents 5

HCID 702EthanolSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

7-(2-Aminoethyl)-4-hydroxy-1,3-benzothiazol-2(3H)-one hydrochloride (176 mg) was dissolved in NMP (2 ml) to give a clear, yellow solution. Sodium hydroxide (27 mg) was dissolved in methanol (0.6 ml), and added in one portion to the yellow solution which turned bright orange. N-[2-(diethylamino)ethyl]-3-[2-(2-naphthyl)ethoxy]-N-(2-oxoethyl)propanamide (Example 32d) (458 mg) was dissolved in DCM (1 ml) and added drop-wise. The mixture was allowed to stir for 1 hour. Sodium triacetoxyborohydride (303 mg) was added portion-wise, and mixture stirred for 45 mins. Water (10 ml) was added followed by DCM, and the layers separated. The aqueous layer was extracted with DCM (×3). The remaining aqueous layer was found to contain desired material, so this was mixed with ethanol, then evaporated to dryness re-dissolved in methanol water mix, and loaded onto a pre-washed SCX cartridge. The cartridge was washed with 1:1 methanol:water, then methanol, then eluted with 0.07N methanolic ammonia to give a yellow film (178 mg). This was dissolved in ethanol, aqueous HBr (100 ul) added and the solution left to stand for 30 mins. The solvents were removed in vacuo to give a yellow solid, which was azeotroped with ethanol (×3). Ethanol was added and mixture sonicated to give a pale yellow suspension. Solid collected by filtration, and washed with ethanol to give the title compound (141 mg).

Workup

  1. customto give a clear, yellow solution
  2. additionadded in one portion to the yellow solution which
  3. additionadded drop-wise
  4. stirringstirred for 45 mins
  5. customthe layers separated
  6. extractionThe aqueous layer was extracted with DCM (×3)
  7. additionso this was mixed with ethanol
  8. customevaporated to dryness
  9. dissolutionre-dissolved in methanol water
  10. additionmix
  11. washThe cartridge was washed with 1:1 methanol
  12. washwater, then methanol, then eluted with 0.07N methanolic ammonia
  13. customto give a yellow film (178 mg)
  14. waitthe solution left
  15. waitto stand for 30 mins
  16. customThe solvents were removed in vacuo
  17. customto give a yellow solid, which
  18. customwas azeotroped with ethanol (×3)
  19. additionEthanol was added
  20. custommixture sonicated
  21. customto give a pale yellow suspension
  22. filtrationSolid collected by filtration
  23. washwashed with ethanol

Sources & evidence

ORD record
ord-4ccd40d992934924ac8dce377359d0d0
Source dataset
uspto-grants-2010_05
Patent number
US07709511B2

Reaction notes

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