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

HRID 503522Notes

Reaction equation

HRID 503522 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.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:38][CH:39]([OH:41])[CH3:40]>>[CH:39]([O:41][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)([CH3:40])[CH3:38]

Participants

4

Reactant 3

HCID 3776IsopropanolHCID 10796Cesium carbonateHCID 866286644-chloro-N-(4-(7-methoxy-1,5-naphthyridin-4-ylthio)phenyl)phthalazin-1-amine

Product 1

HCID 673174434-isopropoxy-N-(4-(7-methoxy-1,5-naphthyridin-4-ylthio)phenyl)phthalazin-1-amine

Procedure

In a 5 mL sealed tube, was dissolved 4-chloro-N-(4-(7-methoxy-1,5-naphthyridin-4-ylthio)phenyl)phthalazin-1-amine (0.100 g, 0.224 mmol) in iPrOH (0.500 mL). To this was added cesium carbonate (0.110 g, 0.336 mmol) and the mixture was irradiated for 30 min at 140° C. in the microwave. When the reaction was determined to be complete by LC/MS, it was concentrated. The mixture concentrate was purified using Isco silica gel chromatography, using 0-100% CH2Cl2:MeOH(90:10)/CH2Cl2, followed by reverse phase chromatography (Gilson, 10-90% TFA/acetonitrile in water over 15 min). The product-containing fractions were extracted into DCM, washed 1× sodium carbonate, 1×H2O, dried with Na2SO4, filtered through fritted funnel, and concentrated to yield 4-isopropoxy-N-(4-(7-methoxy-1,5-naphthyridin-4-ylthio)phenyl)phthalazin-1-amine as a light yellow solid. MS [M+H]+=470.0; Calc'd=469.6 for C26H23N5O2S

Workup

  1. customIn a 5 mL sealed tube
  2. customthe mixture was irradiated for 30 min at 140° C. in the microwave
  3. concentrationwas concentrated
  4. concentrationThe mixture concentrate
  5. customwas purified
  6. customfollowed by reverse phase chromatography (Gilson, 10-90% TFA/acetonitrile in water over 15 min)
  7. extractionThe product-containing fractions were extracted into DCM
  8. washwashed 1× sodium carbonate, 1×H2O
  9. dry with materialdried with Na2SO4
  10. filtrationfiltered through fritted funnel
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-61ba18990b8a4335b4675625c60a1347
Source dataset
uspto-grants-2010_08
Patent number
US07776857B2

Reaction notes

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