Phosgene → N-{5-tert-butyl-2-methoxy-3-[3-(4-pyrrolo[3,2-c]pyridin-1-yl-naphthalen-1-yl)-ureido]-phenyl}-methanesulfonamide

HRID 2417003Notes

Reaction equation

HRID 2417003 reaction equation
[NH2:1][C:2]1[C:3]([O:17][CH3:18])=[C:4]([NH:12][S:13]([CH3:16])(=[O:15])=[O:14])[CH:5]=[C:6]([C:8]([CH3:11])([CH3:10])[CH3:9])[CH:7]=1.[C:19]([O-:22])(O)=O.[Na+].C(Cl)(Cl)=O.[N-]=C=O.[NH2:31][C:32]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[C:35]([N:42]2[C:50]3[CH:49]=[CH:48][N:47]=[CH:46][C:45]=3[CH:44]=[CH:43]2)=[CH:34][CH:33]=1>ClCCl.C1COCC1>[C:8]([C:6]1[CH:7]=[C:2]([NH:1][C:19]([NH:31][C:32]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[C:35]([N:42]3[C:50]4[CH:49]=[CH:48][N:47]=[CH:46][C:45]=4[CH:44]=[CH:43]3)=[CH:34][CH:33]=2)=[O:22])[C:3]([O:17][CH3:18])=[C:4]([NH:12][S:13]([CH3:16])(=[O:15])=[O:14])[CH:5]=1)([CH3:10])([CH3:11])[CH3:9]

Participants

8

Reactant 5

HCID 6371PhosgeneHCID 105034IsocyanateHCID 516892Sodium BicarbonateHCID 10214710N-(3-amino-5-tert-butyl-2-methoxy-phenyl)-methanesulfonamideHCID 114823371-(4-Aminonaphthalen-1-yl)pyrrolo[3,2-c]pyridine

Product 1

HCID 10187755N-{5-tert-butyl-2-methoxy-3-[3-(4-pyrrolo[3,2-c]pyridin-1-yl-naphthalen-1-yl)-ureido]-phenyl}-methanesulfonamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

N-(3-Amino-5-tert-butyl-2-methoxy-phenyl)-methanesulfonamide (75 mg, 0.266 mmol, 1 equiv.) was dissolved in 20 mL dichloromethane and 20 mL of saturated aqueous NaHCO3 solution was added. The biphasic mixture was cooled to 0° C. and phosgene (˜2 M solution in toluene, 0.44 mL) was added to the organic layer via syringe in one portion without stirring. The mixture was then stirred vigorously for 10 min, then the layers were separated. The aqueous layer was extracted once with dichloromethane and the combined organics were dried (Na2SO4), filtered and most of the dichloromethane was removed in vacuo, leaving the toluene. To this isocyanate residue was then added 1-(4-aminonaphthalen-1-yl)pyrrolo[3,2-c]pyridine (Example 1) (46 mg, 0.177 mmol, 1 equiv.) dissolved in 5 mL anhydrous THF. The mixture was left to stir at room temperature overnight, then the solvents were removed in vacuo. The residue was purified by column chromatography on SiO2 using dichloromethane/MeOH eluent mixtures. The title compound (34 mg) was isolated as a pink foam.

Workup

  1. stirringThe mixture was then stirred vigorously for 10 min
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted once with dichloromethane
  4. dry with materialthe combined organics were dried (Na2SO4)
  5. filtrationfiltered and most of the dichloromethane
  6. customwas removed in vacuo
  7. customleaving the toluene
  8. waitThe mixture was left
  9. stirringto stir at room temperature overnight
  10. customthe solvents were removed in vacuo
  11. customThe residue was purified by column chromatography on SiO2

Sources & evidence

ORD record
ord-e25e236bcd844a539d34898266dd436d
Source dataset
uspto-grants-2004_11
Patent number
US06825184B2

Reaction notes

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