tributyl-(1,1-dioxo-4,5-dihydro-1H-1lambda6-thiophen-2-yl)-stannane → HCID 178515429, compound

HRID 1177024Notes

Reaction equation

HRID 1177024 reaction equation
[F:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][N:7]2[C:12](=[O:13])[C:11]([C:14]3[NH:19][C:18]4[CH:20]=[CH:21][C:22](I)=[CH:23][C:17]=4[S:16](=[O:26])(=[O:25])[N:15]=3)=[C:10]([OH:27])[C:9]3=[CH:28][CH:29]=[CH:30][N:8]23)=[CH:4][CH:3]=1.C([Sn](CCCC)(CCCC)[C:38]1[S:39](=[O:44])(=[O:43])[CH2:40][CH2:41][CH:42]=1)CCC>CN(C)C=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[O:43]=[S:39]1(=[O:44])[CH2:40][CH2:41][CH:42]=[C:38]1[C:22]1[CH:21]=[CH:20][C:18]2[NH:19][C:14]([C:11]3[C:12](=[O:13])[N:7]([CH2:6][C:5]4[CH:31]=[CH:32][C:2]([F:1])=[CH:3][CH:4]=4)[N:8]4[CH:30]=[CH:29][CH:28]=[C:9]4[C:10]=3[OH:27])=[N:15][S:16](=[O:26])(=[O:25])[C:17]=2[CH:23]=1

Participants

5

Reactant 2

HCID 59853603tributyl-(1,1-dioxo-4,5-dihydro-1H-1lambda6-thiophen-2-yl)-stannaneHCID 178515433HCID 178515433, compound

Product 1

HCID 178515429HCID 178515429, compoundYield 48.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

1-(4-Fluoro-benzyl)-4-hydroxy-3-(7-iodo-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-pyrrolo[1,2-b]pyridazin-2-one (Example 9b, 0.207 g, 0.371 mmol), tributyl-(1,1-dioxo-4,5-dihydro-1H-1λ6-thiophen-2-yl)-stannane (Example 11a, 0.181 g, 0.442 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.025 g, 0.020 mmol) were dissolved in N,N-dimethylformamide (8 mL) at 25° C. The mixture was heated to 90° C. for 24 h, then was allowed to cool to 25° C. and 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→7% methanol in dichloromethane) to afford a brown solid. This material was re-chromatographed (Merck silica gel 60, 40-63 μm, 40→100% ethyl acetate in hexanes, followed by 100% ethyl acetate, followed by 0→7% methanol in dichloromethane) to afford the desired product, 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 (0.100 g, 0.180 mmol, 48.6% yield). LC-MS (ESI) calcd for C25H19FN4O6S2 554.07. found 555.00 [M+H+].

Workup

  1. temperatureto cool to 25° C.
  2. filtrationfiltered through Celite
  3. concentrationThe filtrate was concentrated in vacuo
  4. customthe residue was purified by flash column chromatography (Merck silica gel 60, 40-63 μm, 0→7% methanol in dichloromethane)
  5. customto afford a brown solid
  6. customThis material was re-chromatographed (Merck silica gel 60, 40-63 μm, 40→100% ethyl acetate in hexanes, followed by 100% ethyl acetate, followed by 0→7% methanol in dichloromethane)

Sources & evidence

ORD record
ord-0a090cb17b6a4fa8aff575212bb37bba
Source dataset
uspto-grants-2010_11
Patent number
US07842838B2

Reaction notes

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