Hydrochloric Acid → N-[3-(4-hydroxy-1-isopentyl-2-oxo-pyrrolo[1,2-b]pyridazin-3-yl)-1,1-dioxo-4H-1$l^{6},4-benzothiazin-7-yl]methanesulfonamide

HRID 2374409Notes

Reaction equation

HRID 2374409 reaction equation
C([O:4][C:5]([C:7]1[N:8]([N:12]([C:18](=[O:37])[CH2:19][C:20]2[NH:25][C:24]3[CH:26]=[CH:27][C:28]([NH:30][S:31]([CH3:34])(=[O:33])=[O:32])=[CH:29][C:23]=3[S:22](=[O:36])(=[O:35])[CH:21]=2)[CH2:13][CH2:14][CH:15]([CH3:17])[CH3:16])[CH:9]=[CH:10][CH:11]=1)=O)C=C.[O-]CC.[Na+].Cl>C(O)C>[OH:4][C:5]1[C:7]2[N:8]([CH:9]=[CH:10][CH:11]=2)[N:12]([CH2:13][CH2:14][CH:15]([CH3:16])[CH3:17])[C:18](=[O:37])[C:19]=1[C:20]1[NH:25][C:24]2[CH:26]=[CH:27][C:28]([NH:30][S:31]([CH3:34])(=[O:33])=[O:32])=[CH:29][C:23]=2[S:22](=[O:35])(=[O:36])[CH:21]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 2723922Sodium ethoxideHCID 598535981-[[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,4]thiazin-3-yl)-acetyl]-(3-methyl-butyl)-amino]-1H-pyrrole-2-carboxylic acid allyl ester

Product 1

HCID 54728267N-[3-(4-hydroxy-1-isopentyl-2-oxo-pyrrolo[1,2-b]pyridazin-3-yl)-1,1-dioxo-4H-1$l^{6},4-benzothiazin-7-yl]methanesulfonamideYield 13.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
60 °C

Procedure

Crude 1-[[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,4]thiazin-3-yl)-acetyl]-(3-methyl-butyl)-amino]-1H-pyrrole-2-carboxylic acid allyl ester (Example 16a, 0.3 mmol) was dissolved in ethanol (3 mL). A 21% solution of sodium ethoxide in ethanol (0.448 mL, 1.2 mmol) was added into the above solution. The mixture was stirred at 60° C. for 4 h. Upon cooling to 25° C., the mixture was poured into 1.0 M aqueous hydrochloric acid solution (50 mL). The aqueous layer was extracted with ethyl acetate (2×50 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo to afford a yellow solid. Purification by flash column chromatography (Teledyne Isco RediSep; 20% ethyl acetate in hexanes to 100% ethyl acetate in hexanes) afforded the desired product, N-{3-[4-hydroxy-1-(3-methyl-butyl)-2-oxo-1,2-dihydro-pyrrolo[1,2-b]pyridazin-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,4]thiazin-7-yl}-methanesulfonamide (20 mg, 0.04 mmol, 13% yield over two steps) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ: 1.05 (6H, d, J=6.6 Hz), 1.64-1.81 (3H, m), 3.11 (3H, s), 4.24-4.31 (2H, m), 5.53 (1H, s), 6.41-6.46 (1H, m), 6.97-7.10 (3H, m), 7.30-7.33 (1H, m), 7.60-7.64 (1H, m), 7.70-7.72 (1H, m). LC-MS (ESI) calcd for C21H24N4O6S2 492.11. found 493.3 [M+H+].

Workup

  1. temperatureUpon cooling to 25° C.
  2. extractionThe aqueous layer was extracted with ethyl acetate (2×50 mL)
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto afford a yellow solid
  7. customPurification by flash column chromatography (Teledyne Isco RediSep; 20% ethyl acetate in hexanes to 100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-d2ca2d26992d475bb1eeebbf0f972ca2
Source dataset
uspto-grants-2008_12
Patent number
US07462611B2

Reaction notes

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