Sodium Methoxide → 4-methoxy-N-(4-(7-methoxy-1,5-naphthyridin-4 ylthio)phenyl)phthalazin-1-amine

HRID 503645Notes

Reaction equation

HRID 503645 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([S:19][C:20]3[C:29]4[C:24](=[CH:25][C:26]([O:30][CH3:31])=[CH:27][N:28]=4)[N:23]=[CH:22][CH:21]=3)=[CH:15][CH:14]=2)=[N:4][N:3]=1.[CH3:32][O-:33].[Na+]>CO>[CH3:32][O:33][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([S:19][C:20]3[C:29]4[C:24](=[CH:25][C:26]([O:30][CH3:31])=[CH:27][N:28]=4)[N:23]=[CH:22][CH:21]=3)=[CH:15][CH:14]=2)=[N:4][N:3]=1

Participants

4

Reactant 2

HCID 10942334Sodium MethoxideHCID 866286644-chloro-N-(4-(7-methoxy-1,5-naphthyridin-4-ylthio)phenyl)phthalazin-1-amine

Product 1

HCID 594273454-methoxy-N-(4-(7-methoxy-1,5-naphthyridin-4 ylthio)phenyl)phthalazin-1-amine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

In a 100 ml RBF was added 4-chloro-N-(4-(7-methoxy-1,5-naphthyridin-4-ylthio)phenyl)phthalazin-1-amine (158 mg, 0.354 mmol) to a solution of sodium methoxide (96 mg, 1.772 mmol) in MeOH. The mixture was heated to reflux with a water condenser attached. The solution was stirred for 16 hours. A white solid precipitated. The mixture was cooled to 0° C., quenched with excess methoxide, followed by saturated NH4Cl, and the resulting solids were filtered and washed with water. The crude solids were purified by Gilson Reverse Phase HPLC eluting with a 15-70% gradient of ACN in water with 0.1% TFA. The product fractions were combined, neutralized with saturated sodium bicarbonate, extracted with 15 ml of methylene chloride (3×), dried organics over Na2SO4, filtered and concentrated filtrate in vacuo to afford 4-methoxy-N-(4-(7-methoxy-1,5-naphthyridin-4 ylthio)phenyl)phthalazin-1-amine as an off-white solid. MS: [M+H]=442.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux with a water condenser
  3. customA white solid precipitated
  4. customquenched with excess methoxide
  5. filtrationthe resulting solids were filtered
  6. washwashed with water
  7. customThe crude solids were purified by Gilson Reverse Phase HPLC
  8. washeluting with a 15-70% gradient of ACN in water with 0.1% TFA
  9. extractionextracted with 15 ml of methylene chloride (3×), dried organics over Na2SO4
  10. filtrationfiltered

Sources & evidence

ORD record
ord-233743e07ef84f56b78331903559ddd3
Source dataset
uspto-grants-2010_08
Patent number
US07776857B2

Reaction notes

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