1,10-Phenanthroline → HCID 178469989, compound

HRID 408759Notes

Reaction equation

HRID 408759 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([C:11](=[NH:23])[NH:12][C:13]2[CH:14]=[CH:15][C:16]3[S:20][CH:19]=[N:18][C:17]=3[C:21]=2Br)[CH:10]=1)=[O:5])[CH3:2].N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>[Cu]I.COCCOC>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([C:11]2[NH:23][C:21]3[C:17]4[N:18]=[CH:19][S:20][C:16]=4[CH:15]=[CH:14][C:13]=3[N:12]=2)[CH:10]=1)=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 13181,10-PhenanthrolineHCID 10796Cesium carbonateHCID 178470005HCID 178470005, compound

Product 1

HCID 178469989HCID 178469989, compoundYield 21%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

The hydrochloride salt of 1-[N-(4-bromo-benzothiazol-5-yl)carbamimidoyl]-1H-pyrazole-4-carboxylic acid ethyl ester (0.128 g, 0.297 mmol), 1,10-phenanthroline (10.7 mg, 59.4 μmol), cesium carbonate (0.290 g, 0.891 mmol), and DME (5.5 mL) were combined in a sealable microwave tube. The tube was sparged with dry nitrogen and copper (I) iodide (5.70 mg, 29.7 μmol) was added. The reaction mixture was further sparged and the tube was sealed and heated at 80° C. for 1.75 h. The reaction mixture was partitioned between 1M aq. HCl (15 mL) and EtOAc (25 mL). The aqueous layer was further extracted with EtOAc (2×20 mL) and the combined organic layers were washed with brine (10 mL), dried, filtered, and concentrated under reduced pressure. The residue was purified (FCC) (10-60% EtOAc/hexanes, dry-loaded), the clean fractions were concentrated and the residue triturated with diethyl ether to yield the titled compound (19.5 mg, 21% yield). MS (ESI/CI): mass calcd. for C14H11N6O2S, 313.1; m/z found, 314.1 [M+H]+. 1H NMR (400 MHz, DMSO-d6): 13.75 (s, 1H), 9.45 (s, 1H), 9.05 (s, 1H), 8.37 (s, 1H), 8.00 (d, J=8.6 Hz, 1H), 7.65 (d, J=6.0 Hz, 1H), 4.31 (q, J=7.0 Hz, 2H), 1.34 (t, J=7.1 Hz, 3H).

Workup

  1. additionwas added
  2. customThe reaction mixture was further sparged
  3. customthe tube was sealed
  4. customThe reaction mixture was partitioned between 1M aq. HCl (15 mL) and EtOAc (25 mL)
  5. extractionThe aqueous layer was further extracted with EtOAc (2×20 mL)
  6. washthe combined organic layers were washed with brine (10 mL)
  7. customdried
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified (FCC) (10-60% EtOAc/hexanes, dry-loaded)
  11. concentrationthe clean fractions were concentrated
  12. customthe residue triturated with diethyl ether

Sources & evidence

ORD record
ord-bbe8beea8ca645b0b1f81792e1aabf85
Source dataset
uspto-grants-2014_06
Patent number
US08759345B2

Reaction notes

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