Diethyl Ether → HCID 178515430, compound

HRID 730520Notes

Reaction equation

HRID 730520 reaction equation
[O:1]=[S:2]1(=[O:38])[CH2:6][CH2:5][CH:4]=[C:3]1[C:7]1[CH:37]=[CH:36][C:10]2[NH:11][C:12]([C:17]3[C:22](=[O:23])[N:21]([CH2:24][C:25]4[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=4)[N:20]4[CH:32]=[CH:33][CH:34]=[C:19]4[C:18]=3[OH:35])=[N:13][S:14](=[O:16])(=[O:15])[C:9]=2[CH:8]=1.[H][H].C(OCC)C>CN(C)C=O.[Pd]>[O:38]=[S:2]1(=[O:1])[CH2:6][CH2:5][CH2:4][CH:3]1[C:7]1[CH:37]=[CH:36][C:10]2[NH:11][C:12]([C:17]3[C:22](=[O:23])[N:21]([CH2:24][C:25]4[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=4)[N:20]4[CH:32]=[CH:33][CH:34]=[C:19]4[C:18]=3[OH:35])=[N:13][S:14](=[O:16])(=[O:15])[C:9]=2[CH:8]=1

Participants

6

Reactant 3

HCID 3283Diethyl EtherHCID 178418361HCID 178418361, compoundHCID 178515429HCID 178515429, compound

Product 1

HCID 178515430HCID 178515430, compoundYield 28%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

3-[7-(1,1-Dioxo-4,5-dihydro-1H-1λ6-thiophen-2-yl)-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl]-1-(4-fluoro-benzyl)-4-hydroxy-pyrrolo[1,2-b]pyridazin-2-one (Example 11b, 0.100 g, 0.180 mmol) was dissolved in N,N-dimethylformamide (15 mL) at 25° C. Palladium on carbon (5%, 0.250 g) was added and the atmosphere in the reaction flask replaced with hydrogen from a balloon. After stirring for 1 h under a hydrogen balloon, the mixture was filtered through Celite. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography (Merck silica gel 60, 40-63 μm, 0→3% methanol in dichloromethane) to afford a yellow solid. Trituration of this material with diethyl ether afforded the desired product, 3-[7-(1,1-dioxo-tetrahydro-1λ6-thiophen-2-yl)-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl]-1-(4-fluoro-benzyl)-4-hydroxy-pyrrolo[1,2-b]pyridazin-2-one (0.028 g, 0.050 mmol, 28% yield). 1H NMR (400 MHz, DMSO-d6) δ: 2.08-2.18 (1H, m), 2.23-2.29 (1H, m), 2.32-2.43 (1H, m), 3.20-3.28 (1H, m), 3.31-3.37 (1H, m), 4.56-4.61 (1H, m), 5.65 (2H, s), 6.60 (2H, d, J=7.0 Hz), 6.59-6.61 (1H, m), 7.02-7.03 (1H, m), 7.14-7.18 (2H, m), 7.42-7.46 (1H, m), 7.67-7.75 (2H, m), 7.87 (1H, bs), 13.73 (1H, s). LC-MS (ESI) calcd for C25H21FN4O6S2 556.09, found 557.15 [M+H+].

Workup

  1. filtrationthe mixture was filtered through Celite
  2. concentrationThe filtrate was concentrated in vacuo
  3. customthe residue was purified by flash column chromatography (Merck silica gel 60, 40-63 μm, 0→3% methanol in dichloromethane)
  4. customto afford a yellow solid

Sources & evidence

ORD record
ord-5559356123614187862f0d81ea6f1154
Source dataset
uspto-grants-2009_09
Patent number
US07582754B2

Reaction notes

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