Hydrochloric Acid → HCID 178504987, compound

HRID 1177056Notes

Reaction equation

HRID 1177056 reaction equation
C([O:4][C:5]([C:7]1[N:8]([N:12]([CH2:33][C:34]2[CH:39]=[CH:38][C:37]([F:40])=[C:36]([Cl:41])[CH:35]=2)[C:13](=[O:32])[CH2:14][C:15]2[NH:20][C:19]3[CH:21]=[CH:22][C:23](CS(C)(=O)=O)=[CH:24][C:18]=3[S:17](=[O:31])(=[O:30])[N:16]=2)[CH:9]=[CH:10][CH:11]=1)=O)C=C.[O-]CC.[Na+].Cl>C(O)C.C(OCC)(=O)C>[Cl:41][C:36]1[CH:35]=[C:34]([CH:39]=[CH:38][C:37]=1[F:40])[CH2:33][N:12]1[C:13](=[O:32])[C:14]([C:15]2[NH:20][C:19]3[CH:21]=[CH:22][C:23]([NH:16][S:17]([CH3:18])(=[O:31])=[O:30])=[CH:24][C:18]=3[S:17](=[O:31])(=[O:30])[N:16]=2)=[C:5]([OH:4])[C:7]2=[CH:11][CH:10]=[CH:9][N:8]12

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 2723922Sodium ethoxideHCID 68776310HCID 68776310, compound

Product 1

HCID 178504987HCID 178504987, compoundYield 63.9%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 1-{(3-chloro-4-fluoro-benzyl)-[2-(7-methanesulfonylmethyl-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-1H-pyrrole-2-carboxylic acid allyl ester (Example 17i, 304.5 mg, 0.488 mmol) in absolute ethanol (5 mL) was added a 21% solution of sodium ethoxide in ethanol (1.1 mL, 2.95 mmol). After stirring at 60° C. for 12 h, the mixture was diluted with ethyl acetate and acidified with 1.0 M aqueous hydrochloric acid solution upon which a precipitate formed. The solid was collected by vacuum filtration to afford the desired product, N-{3-[1-(3-chloro-4-fluoro-benzyl)-4-hydroxy-2-oxo-1,2-dihydro-pyrrolo[1,2-b]pyridazin-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide (88.5 mg, 0.156 mmol, 32% yield) as an off-white solid. The filtrate was extracted with ethyl acetate (2×20 mL). The combined organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The crude mixture was purified by HPLC purification (Column Luna 5μ C18 (2) 100 Å AXIA 150×21.2 mm, 5 micron, 25%-100% in 12 min 30 mL/min flow rate, 0.05% trifluoroacetic acid in acetonitrile/0.05% trifluoroacetic acid in water) to afford more of the desired product, N-{3-[1-(3-chloro-4-fluoro-benzyl)-4-hydroxy-2-oxo-1,2-dihydro-pyrrolo[1,2-b]pyridazin-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide (18.4 mg, 0.033 mmol, 7% yield; total 39% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 3.06 (3H, s), 5.61 (2H, s), 6.57 (1H, s), 6.98 (1H, s), 7.37 (2H, d, J=7.6 Hz), 7.52 (1H, dd, J1=8.5 Hz, J2=2.4 Hz), 7.59-7.68 (4H, m), 10.17 (1H, s). LC-MS (ESI) calcd for C22H17ClFN5O6S2 565.03. found 566.2 [M+H+].

Workup

  1. customformed
  2. filtrationThe solid was collected by vacuum filtration

Sources & evidence

ORD record
ord-dd110a8bf88b45389c0b70d8547bb5f2
Source dataset
uspto-grants-2010_11
Patent number
US07842838B2

Reaction notes

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