Cesium carbonate → N-(4-(7-methoxy-1,5-naphthyridin-4-yloxy)phenyl)-4-(4-(2-(triethylsilyl)ethynyl)phenyl)phthalazin-1-amine

HRID 503571Notes

Reaction equation

HRID 503571 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][C:26]4[C:35]5[C:30](=[CH:31][C:32]([O:36][CH3:37])=[CH:33][N:34]=5)[N:29]=[CH:28][CH:27]=4)=[CH:21][CH:20]=3)=[N:10][N:9]=2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[CH2:78]([Si:80]([C:85]#[CH:86])([CH2:83][CH3:84])[CH2:81][CH3:82])[CH3:79]>C(#N)C.C(#N)C.C(#N)C.Cl[Pd]Cl.O1CCOCC1>[CH3:37][O:36][C:32]1[CH:31]=[C:30]2[C:35]([C:26]([O:25][C:22]3[CH:21]=[CH:20][C:19]([NH:18][C:11]4[C:12]5[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=5)[C:8]([C:5]5[CH:6]=[CH:7][C:2]([C:86]#[C:85][Si:80]([CH2:83][CH3:84])([CH2:81][CH3:82])[CH2:78][CH3:79])=[CH:3][CH:4]=5)=[N:9][N:10]=4)=[CH:24][CH:23]=3)=[CH:27][CH:28]=[N:29]2)=[N:34][CH:33]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 637947(Triethylsilyl)acetyleneHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 24983554HCID 24983554, compound

Product 1

HCID 67316053N-(4-(7-methoxy-1,5-naphthyridin-4-yloxy)phenyl)-4-(4-(2-(triethylsilyl)ethynyl)phenyl)phthalazin-1-amine

Reagents, catalysts & solvents 3

HCID 6093782Bis(acetonitrile)dichloropalladiumCatalystHCID 6342AcetonitrileSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

In an argon purged sealed pressure vessel was added 4-(4-chlorophenyl)-N-(4-(7-methoxy-1,5-naphthyridin-4-yloxy)phenyl)phthalazin-1-amine (0.120 g, 0.237 mmol), cesium carbonate (0.201 g, 0.617 mmol), X-phos (0.017 g, 0.0356 mmol), dichloropalladium bisacetonitrile (0.003 mg, 0.011 mmol), and acetonitrile (0.50 mL). Starting material was not soluble in acetonitrile, so added 0.5 mL 1,4 dioxane. Purged the reaction with argon, then added (triethylsilyl)acetylene (0.055 mL, 0.308 mmol), and again purged with vessel with argon, sealed, heated it to 90° C. The reaction was stirred for 1 h. Reaction complete by LC/MS. The reaction was cooled to RT, passed through pad of silica, washed with 100% CH2Cl2:MeOH(90:10)/CH2Cl2 and the organics were concentrated. The crude material was purified by silica gel chromatography eluting with 0-100% CH2Cl2:MeOH(90:10)/CH2Cl2. The product fractions were concentrated to yield N-(4-(7-methoxy-1,5-naphthyridin-4-yloxy)phenyl)-4-(4-(2-(triethylsilyl)ethynyl)phenyl)phthalazin-1-amine as light yellow solid. MS [M+H]=610.2; Calc'd 609.8 for C37H35N5O2Si.

Workup

  1. customIn an argon purged
  2. customsealed pressure vessel
  3. customPurged
  4. customthe reaction with argon
  5. customsealed
  6. customReaction complete by LC/MS
  7. temperatureThe reaction was cooled to RT
  8. washwashed with 100% CH2Cl2:MeOH(90:10)/CH2Cl2
  9. concentrationthe organics were concentrated
  10. customThe crude material was purified by silica gel chromatography
  11. washeluting with 0-100% CH2Cl2:MeOH(90:10)/CH2Cl2
  12. concentrationThe product fractions were concentrated

Sources & evidence

ORD record
ord-faccbb01fcbd418a8041f36345e1236b
Source dataset
uspto-grants-2010_08
Patent number
US07776857B2

Reaction notes

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