(S)-3,4-Dihydro-4-hydroxy-2-(3-methoxypropyl)-2H-thieno[3,2-e]-1,2-thiazine-6-sulfonamide 1,1-dioxide Chemical Properties

Melting point:

112-115oC

Boiling point:

612.4±65.0 °C(Predicted)

Density 

1.575±0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

solubility 

DMSO (Slightly), Methanol (Slightly)

form 

Solid

pka

9.53±0.40(Predicted)

color 

White to Off-White

InChI

InChI=1S/C10H16N2O6S3/c1-18-4-2-3-12-6-8(13)7-5-9(20(11,14)15)19-10(7)21(12,16)17/h5,8,13H,2-4,6H2,1H3,(H2,11,14,15)/t8-/m1/s1

InChIKey

UHIWBQIWXWWDKT-MRVPVSSYSA-N

SMILES

S1(=O)(=O)C2SC(S(N)(=O)=O)=CC=2[C@H](O)CN1CCCOC

(S)-3,4-Dihydro-4-hydroxy-2-(3-methoxypropyl)-2H-thieno[3,2-e]-1,2-thiazine-6-sulfonamide 1,1-dioxide Usage And Synthesis

Uses

(S)-4-Hydroxy-2-(3-methoxypropyl)-3,4-dihydro-2H-thieno[3,2-e][1,2]thiazine-6-sulfonamide 1,1-Dioxide has been used as a reactant for the preparation of Brinzolamide (AL-4862) [B677600], a topical carbonic anhydrase inhibitor.

Synthesis

The general procedure for the synthesis of (S)-3,4-dihydro-4-hydroxy-2-(3-methoxypropyl)-2H-thieno[3,2-e]-1,2-thiazine-6-sulfonamide 1,1-dioxide from the compound (CAS: 1245550-91-7) is as follows: the cyclization reaction of the compound (VI) can be carried out with a chiral reductant, e.g., (+)-diisopropylphenylborane (DIPCI) to obtain a single isomer of the target compound (VII) by stereoselective reduction. The procedure was as follows: compound (VI) (210 g, 0.484 mol) was suspended in tert-butyl methyl ether (15 v/v) and stirred under nitrogen protection. The suspension was cooled to -40 °C and (+)-diisopropylaminoborane (DIPCI) (762 g, 60-65% hexane solution, 1.063 mol) was slowly added through a cannula over 30 min. The temperature was raised to -30 °C during the reaction. The reaction mixture was maintained at -25 to -20 °C for 3.0 to 4.0 h. The reaction progress was monitored by TLC (mobile phase: ethyl acetate:hexane = 3:7). After completion of the reduction reaction, 1M aqueous sodium hydroxide solution (20 vol) was added through the addition funnel within 15-20 minutes. The reaction mixture was stirred at 25-30°C overnight and the completion of the reaction was monitored by TLC (mobile phase: ethyl acetate:hexane=1:1). Upon completion of the reaction, the aqueous and organic phases were separated, and the aqueous phase was extracted with tert-butyl methyl ether (4.0 v/v), followed by acidification to pH 1 with 5N hydrochloric acid solution, and extraction with ethyl acetate (3 x 6.0 v/v). The ethyl acetate extracts were combined, washed with saturated brine solution (2 x 2.5 volumes), dried over sodium sulfate and filtered. The organic layer was completely distilled under reduced pressure (at a temperature below 50°C) to give a light yellow syrupy crude product. The yield of compound (VII) was 112 g (65.2% yield). Alternatively, step (f) can be carried out using a non-chiral reducing agent such as sodium tetrahydroborane, subject to a subsequent optical splitting step to remove unwanted isomers.

References

[1] Patent: WO2010/103115, 2010, A1. Location in patent: Page/Page column 15-16

(S)-3,4-Dihydro-4-hydroxy-2-(3-methoxypropyl)-2H-thieno[3,2-e]-1,2-thiazine-6-sulfonamide 1,1-dioxide(154127-42-1)Related Product Information

• N-[4-Cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)thio]-2-hydroxy-2-methylpropionamide
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