Sarcosine → HCID 178446175, compound

HRID 1177037Notes

Reaction equation

HRID 1177037 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9]([OH:10])=[C:8]([C:11]3[NH:16][C:15]4[CH:17]=[CH:18][C:19](I)=[CH:20][C:14]=4[S:13](=[O:23])(=[O:22])[N:12]=3)[C:7](=[O:24])[N:6]([CH2:25][CH2:26][CH:27]([CH3:29])[CH3:28])[N:5]2[CH:30]=1.[O-]P(OP(OP([O-])([O-])=O)([O-])=O)(=O)[O-].[K+].[K+].[K+].[K+].[K+].N(CC(O)=O)C.[CH3:55][S:56]([NH2:59])(=[O:58])=[O:57]>[Cu]I.CN(C)C=O>[F:1][C:2]1[CH:3]=[C:4]2[C:9]([OH:10])=[C:8]([C:11]3[NH:16][C:15]4[CH:17]=[CH:18][C:19]([NH:59][S:56]([CH3:55])(=[O:58])=[O:57])=[CH:20][C:14]=4[S:13](=[O:23])(=[O:22])[N:12]=3)[C:7](=[O:24])[N:6]([CH2:25][CH2:26][CH:27]([CH3:29])[CH3:28])[N:5]2[CH:30]=1

Participants

7

Reactant 4

HCID 1088SarcosineHCID 61695Pentapotassium TriphosphateHCID 72879MethanesulfonamideHCID 178446171HCID 178446171, compound

Product 1

HCID 178446175HCID 178446175, compoundYield 15.5%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

6-Fluoro-4-hydroxy-3-(7-iodo-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-1-(3-methyl-butyl)-pyrrolo[1,2-b]pyridazin-2-one (Example 14j, 0.047 g, 0.086 mmol), potassium triphosphate (0.055 g, 0.258 mmol), sarcosine (0.0046 g, 0.0516 mmol), and copper (I) iodide (0.0066 g, 0.0344 mmol) were combined. Anhydrous N,N-dimethylformamide (3 mL) was added followed by methanesulfonamide (0.0245 g, 0.258 mmol). The flask was purged with nitrogen and the mixture was stirred at 100° C. for 16 h. Upon cooling, the mixture was filtered over Celite, washed with ethyl acetate and the solvent was removed in vacuo. Purification by preparative HPLC (Column Luna 5μ C18 (2) 100 Å size 150×21.2 mm, 5 micron, 40%-95% in 11 min 25 mL/min flow rate, 0.05% trifluoroacetic acid in acetonitrile/0.05% trifluoroacetic acid in water) afforded the desired product, N-{3-[6-fluoro-4-hydroxy-1-(3-methyl-butyl)-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 (0.0068 g, 0.0133 mmol, 15.4% yield) as a solid. 1H NMR (400 MHz, DMSO-d6) δ: 0.96 (3H, s), 0.97 (3H, s), 1.53-1.59 (2H, m), 1.66-1.76 (1H, m), 3.07 (3H, s), 4.32 (2H, t, J=7.5 Hz), 6.83 (1H, bs), 7.51-7.63 (3H, m), 8.06 (1H, bs), 10.17 (1H, bs). LC-MS (ESI) calcd for C20H22FN5O6S2 511.10. found 512.3 [M+H+].

Workup

  1. customThe flask was purged with nitrogen
  2. temperatureUpon cooling
  3. filtrationthe mixture was filtered over Celite
  4. washwashed with ethyl acetate
  5. customthe solvent was removed in vacuo
  6. customPurification by preparative HPLC (Column Luna 5μ C18 (2) 100 Å size 150×21.2 mm, 5 micron, 40%-95% in 11 min 25 mL/min flow rate, 0.05% trifluoroacetic acid in acetonitrile/0.05% trifluoroacetic acid in water)

Sources & evidence

ORD record
ord-12e2ea79ac80404c93c84df7513aba83
Source dataset
uspto-grants-2010_11
Patent number
US07842838B2

Reaction notes

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