3-[bis(methylsulfanyl)methylene]-1-isopentyl-2,4(1H,3H)-pyridinedione → 3-(7-amino-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-1-isopentyl-2(1H)-pyridinone

HRID 601421Notes

Reaction equation

CS[C:3](SC)=[C:4]1[C:9](=[O:10])[CH:8]=[CH:7][N:6]([CH2:11][CH2:12][CH:13]([CH3:15])[CH3:14])[C:5]1=[O:16].[NH2:19][C:20]1[CH:25]=[CH:24][C:23]([NH:26]C(=O)OC(C)(C)C)=[CH:22][C:21]=1[S:34]([NH2:37])(=[O:36])=[O:35]>O1CCOCC1>[NH2:26][C:23]1[CH:24]=[CH:25][C:20]2[NH:19][C:3]([C:4]3[C:5](=[O:16])[N:6]([CH2:11][CH2:12][CH:13]([CH3:14])[CH3:15])[CH:7]=[CH:8][C:9]=3[OH:10])=[N:37][S:34](=[O:36])(=[O:35])[C:21]=2[CH:22]=1

Participants

Conditions

Temperature: 25 °C

Procedure

The product of Example 457C (2.08 g, 7.29 mmol) was treated with the product of Example 414A (2.00 g, 6.96 mmol) in dioxane (20 mL) at 115° C. for 30 minutes, cooled to 25° C. and concentrated under reduced pressure. A solution of the residue in 4M hydrochloric acid in dioxane (20 mL) was stirred at 25° C. for 18 hours and concentrated under reduced pressure. The residue was triturated with dichloromethane and filtered to give the title compound. The filtrate containing the protected intermediate was concentrated and purified by chromatography on silica gel eluting with 1% methanol in dichloromethane. The protected product was re-subjected to the above deprotection conditions to provide the title compound as its hydrochloride salt (2.02 g, 96%). 1H NMR (300 MHz, DMSO-d6) δ 0.92 (s, 3 H) 0.94 (s, 3 H) 1.58 (m, 3 H) 3.99 (m, 2 H) 6.31 (d, J=7.35 Hz, 1 H) 6.96 (m, 2 H) 7.34 (d, J=8.46 Hz, 1 H) 8.04 (d, J=7.35 Hz, 1 H) 14.04 (s, 1 H) 14.19 (s, 1 H). MS (ESI−) m/z 375 (M−H)−.

Workup

concentrationconcentrated under reduced pressure
concentrationconcentrated under reduced pressure
customThe residue was triturated with dichloromethane
filtrationfiltered

Sources & evidence

ORD record: ord-da8a6508cbcd4108856087f3625c0017
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07902203B2

Reaction notes

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