Sarcosine → HCID 178504986, compound

HRID 730516Notes

Reaction equation

HRID 730516 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.P([O-])([O-])([O-])=O.[K+].[K+].[K+].N(CC(O)=O)C.[CH3:47][S:48]([NH2:51])(=[O:50])=[O:49]>CN(C)C=O.C(OCC)(=O)C.[Cu]I.C(OCC)C.CO>[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]([NH:51][S:48]([CH3:47])(=[O:50])=[O:49])=[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

Participants

10

Reactant 4

HCID 1088SarcosineHCID 62657Potassium Phosphate, TribasicHCID 72879MethanesulfonamideHCID 178515433HCID 178515433, compound

Product 1

HCID 178504986HCID 178504986, compoundYield 47%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °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, 0.257 g, 0.455 mmol), potassium phosphate (tribasic) (0.483 g, 2.28 mmol), copper(I) iodide (0.022 g, 0.11 mmol), sarcosine (0.024 g, 0.273 mmol, and methanesulfonamide (0.433 g, 4.55 mmol) were dissolved in N,N-dimethylformamide (9 mL) at 25° C. The mixture was heated to 100° C. for 6 h, then was allowed to cool to 25° C., diluted with ethyl acetate (10 mL), 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→10% methanol in dichloromethane) to afford a yellow solid. Sequential trituration of this material with methanol and diethyl ether afforded the desired product, N-{3-[1-(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 (0.113 g, 0.21 mmol, 47% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ: 3.08 (3H, s), 5.65 (2H, s), 6.59-6.61 (1H, m), 7.01-7.02 (1H, m), 7.14-7.18 (2H, m), 7.42-7.46 (2H, m), 7.54 (1H, dd, J1=2.3 Hz, J2=8.6 Hz), 7.62 (1H, d, J=2.5 Hz), 7.66 (1H, d, J=8.9 Hz), 7.71 (1H, s), 10.21 (1H, s), 13.66 (1H, s). LC-MS (ESI) calcd for C22H18FN5O6S2 531.07, found 532.10 [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→10% methanol in dichloromethane)
  5. customto afford a yellow solid

Sources & evidence

ORD record
ord-d393ec1239dc47bea82e2fa2bde67e80
Source dataset
uspto-grants-2009_09
Patent number
US07582754B2

Reaction notes

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