Triethylamine → HCID 59853592, compound

HRID 1177010Notes

Reaction equation

HRID 1177010 reaction equation
O.NN.[S:4]1[C:8]2[CH:9]=[C:10]([N:13]([CH3:18])[S:14]([CH3:17])(=[O:16])=[O:15])[CH:11]=[CH:12][C:7]=2[N:6]=C1.C(N(CC)CC)C.[CH3:26][O:27][C:28](=[O:34])[CH2:29][C:30](=O)[CH2:31]Cl>C(O)C.O1CCCC1>[CH3:26][O:27][C:28](=[O:34])[CH2:29][C:30]1[NH:6][C:7]2[CH:12]=[CH:11][C:10]([N:13]([S:14]([CH3:17])(=[O:15])=[O:16])[CH3:18])=[CH:9][C:8]=2[S:4][CH:31]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 24654Hydrazine hydrate (1:1)HCID 36240Methyl 4-chloroacetoacetateHCID 59853593HCID 59853593, compound

Product 1

HCID 59853592HCID 59853592, compoundYield 64%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

Hydrazine monohydrate (20.1 mL, 414 mmol) was added to a solution of N-benzothiazol-6-yl-N-methyl-methanesulfonamide (Example 7b, 10.06 g, 41.5 mmol) in ethanol (150 mL) at 25° C. The reaction mixture was heated to 50° C. for 13 h, and then was concentrated in vacuo. The residue was dissolved in 1.0 M aqueous hydrochloric acid solution (100 mL) and the pH was adjusted to 7 by the addition of 6.0 M aqueous hydrochloric acid solution. The resulting mixture was extracted with ethyl acetate (2×150 mL) and the aqueous layer was acidified to pH 3 by the addition of 6.0 M aqueous hydrochloric acid solution, and then neutralized to pH 7 by the addition of solid sodium bicarbonate. The mixture was again extracted with ethyl acetate (1×150 mL) and all organic layers were combined, dried over sodium sulfate, filtered and concentrated in vacuo. The orange solid thus obtained was dissolved in tetrahydrofuran (150 mL) and triethylamine (12.3 mL, 88.2 mmol), and 4-chloro-3-oxo-butyric acid methyl ester (5.10 mL, 44.2 mmol) were added sequentially at 25° C. The reaction mixture was stirred at 25° C. for 2 h, and then was partitioned between 1.0 M aqueous hydrochloric acid solution (150 mL) and ethyl acetate (2×150 mL). The organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. Purification of the residue by flash column chromatography (Merck silica gel 60, 40-63 μm, 20→100% ethyl acetate in hexanes) afforded the desired product, [7-(methanesulfonyl-methyl-amino)-4H-benzo[1,4]thiazin-3-yl]-acetic acid methyl ester (8.40 g, 25.6 mmol, 64% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ: 2.86 (3H, s), 3.27 (3H, s), 3.43 (2H, s), 3.72 (3H, s), 6.86 (1H, d, J=8.6 Hz), 7.12 (1H, dd, J1=2.3 Hz, J2=8.6 Hz), 7.21 (1H, d, J=2.4 Hz), 10.63 (1H, s).

Workup

  1. concentrationwas concentrated in vacuo
  2. dissolutionThe residue was dissolved in 1.0 M aqueous hydrochloric acid solution (100 mL)
  3. additionthe pH was adjusted to 7 by the addition of 6.0 M aqueous hydrochloric acid solution
  4. extractionThe resulting mixture was extracted with ethyl acetate (2×150 mL)
  5. additionthe aqueous layer was acidified to pH 3 by the addition of 6.0 M aqueous hydrochloric acid solution
  6. additionneutralized to pH 7 by the addition of solid sodium bicarbonate
  7. extractionThe mixture was again extracted with ethyl acetate (1×150 mL)
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe orange solid thus obtained
  12. customwas partitioned between 1.0 M aqueous hydrochloric acid solution (150 mL) and ethyl acetate (2×150 mL)
  13. dry with materialThe organic layers were dried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo
  16. customPurification of the residue by flash column chromatography (Merck silica gel 60, 40-63 μm, 20→100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-567db81a403e416a8c233f3f98a5ceec
Source dataset
uspto-grants-2010_11
Patent number
US07842838B2

Reaction notes

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