Sarcosine → HCID 178446177, compound

HRID 730522Notes

Reaction equation

HRID 730522 reaction equation
[OH:1][C:2]1[C:3]2[N:4]([CH:27]=[CH:28][CH:29]=2)[N:5]([CH2:22][CH2:23][CH:24]([CH3:26])[CH3:25])[C:6](=[O:21])[C:7]=1[C:8]1[NH:13][C:12]2[CH:14]=[CH:15][C:16](I)=[CH:17][C:11]=2[S:10](=[O:20])(=[O:19])[N:9]=1.[O-]P(OP(OP([O-])([O-])=O)([O-])=O)(=O)[O-].[K+].[K+].[K+].[K+].[K+].N(CC(O)=O)C.[CH:54]1([S:57]([NH2:60])(=[O:59])=[O:58])[CH2:56][CH2:55]1>[Cu]I.CN(C)C=O>[OH:1][C:2]1[C:3]2[N:4]([CH:27]=[CH:28][CH:29]=2)[N:5]([CH2:22][CH2:23][CH:24]([CH3:26])[CH3:25])[C:6](=[O:21])[C:7]=1[C:8]1[NH:13][C:12]2[CH:14]=[CH:15][C:16]([NH:60][S:57]([CH:54]3[CH2:56][CH2:55]3)(=[O:59])=[O:58])=[CH:17][C:11]=2[S:10](=[O:20])(=[O:19])[N:9]=1

Participants

7

Reactant 4

HCID 1088SarcosineHCID 61695Pentapotassium TriphosphateHCID 15765418CyclopropanesulfonamideHCID 178446170HCID 178446170, compound

Product 1

HCID 178446177HCID 178446177, compoundYield 50.3%

Reagents, catalysts & solvents 2

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

Procedure

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 13a, 0.105 g, 0.199 mmol), potassium triphosphate (0.127 g, 0.598 mmol), sarcosine (0.011 g, 0.119 mmol), and copper (I) iodide (0.015 g, 0.080 mmol) were combined. Anhydrous N,N-dimethylformamide (7 mL) was added followed by cyclopropanesulfonic acid amide (0.12 g, 1 mmol). The solution was degassed while stirring under vacuum and the flask purged with nitrogen. The mixture was stirred at 100° C. for 16 h. Upon cooling, the mixture was diluted with ethyl acetate (200 mL), washed with 1.0 M aqueous hydrochloric acid solution (2×100 mL), dried over magnesium sulfate, filtered and concentrated in vacuo to a solid. Purification by HPLC (Column Luna 5u C18 (2) 100 Å size 50×21.2 mm, 5 micron, 40%-95% 0.05% trifluoroacetic acid in acetonitrile/0.05% trifluoroacetic acid in water) afforded the desired product, cyclopropanesulfonic acid {3-[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}-amide (0.052 g, 0.10 mmol, 50% yield) as a pale yellow powder. 1H NMR (400 MHz, DMSO-d6) δ: 0.97 (10H, m), 1.51 (2H, q, J=7.2 Hz), 1.73 (1H, m), 2.71 (1H, m), 4.41 (2H, t, J=7.6 Hz), 6.72 (1H, m), 7.02 (1H, d, J=3.6 Hz), 7.58 (1H, m), 7.63 (2H, m), 7.88 (1H, s), 10.12 (1H, bs). LC-MS (ESI) calcd for C22H25N5O6S2, found 519.12, found 520.3 [M+H+].

Workup

  1. customThe solution was degassed
  2. customthe flask purged with nitrogen
  3. stirringThe mixture was stirred at 100° C. for 16 h
  4. temperatureUpon cooling
  5. additionthe mixture was diluted with ethyl acetate (200 mL)
  6. washwashed with 1.0 M aqueous hydrochloric acid solution (2×100 mL)
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo to a solid
  10. customPurification by HPLC (Column Luna 5u C18 (2) 100 Å size 50×21.2 mm, 5 micron, 40%-95% 0.05% trifluoroacetic acid in acetonitrile/0.05% trifluoroacetic acid in water)

Sources & evidence

ORD record
ord-13d84c28835e48dda7fc5a4cf7fbd00b
Source dataset
uspto-grants-2009_09
Patent number
US07582754B2

Reaction notes

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