Potassium Carbonate → tert-Butyl 5-fluoro-4-(2-(4-(4-phenylphthalazin-1-ylamino)phenoxy)pyridin-3-yl)pyrimidin-2-ylcarbamate

HRID 593999Notes

Reaction equation

HRID 593999 reaction equation
CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.O1CCOCC1.Cl[C:50]1[N:55]=[C:54]([C:56]2[C:57]([O:62][C:63]3[CH:68]=[CH:67][C:66]([NH:69][C:70]4[C:79]5[C:74](=[CH:75][CH:76]=[CH:77][CH:78]=5)[C:73]([C:80]5[CH:85]=[CH:84][CH:83]=[CH:82][CH:81]=5)=[N:72][N:71]=4)=[CH:65][CH:64]=3)=[N:58][CH:59]=[CH:60][CH:61]=2)[C:53]([F:86])=[CH:52][N:51]=1.[C:87](=[O:94])([O:89][C:90]([CH3:93])([CH3:92])[CH3:91])[NH2:88].C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CO>[F:86][C:53]1[C:54]([C:56]2[C:57]([O:62][C:63]3[CH:68]=[CH:67][C:66]([NH:69][C:70]4[C:79]5[C:74](=[CH:75][CH:76]=[CH:77][CH:78]=5)[C:73]([C:80]5[CH:85]=[CH:84][CH:83]=[CH:82][CH:81]=5)=[N:72][N:71]=4)=[CH:65][CH:64]=3)=[N:58][CH:59]=[CH:60][CH:61]=2)=[N:55][C:50]([NH:88][C:87](=[O:94])[O:89][C:90]([CH3:93])([CH3:92])[CH3:91])=[N:51][CH:52]=1

Participants

10

Reactant 5

HCID 11430Potassium CarbonateHCID 312751,4-Dioxane2×HCID 77922tert-Butyl carbamateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86614169N-(4-(3-(2-chloro-5-fluoropyrimidin-4-yl)pyridin-2-yloxy)phenyl)-4-phenylphthalazin-1-amine

Product 1

HCID 66731483tert-Butyl 5-fluoro-4-(2-(4-(4-phenylphthalazin-1-ylamino)phenoxy)pyridin-3-yl)pyrimidin-2-ylcarbamate

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 86614170Pd(OAc)2 XantphosCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
110 °C

Procedure

The title compound was prepared according to the procedure described in Garnier, E.; Andoux, J.; Pasquinet, E.; Suzenet, F.; Poullain, D.; Lebret, B.; Guillaumet, G. J. Org. Chem. 2004, 69, 7809. Xantphos (281 mg, 486 μmol) and 1,4-dioxane (12151 μl, 2430 μmol) were added into a sealed tube. The tube was purged with argon, then palladium(II) acetate (55.0 mg, 243 μmol) was added. The mixture was stirred under argon for 10 min. In a separate sealed tube, N-(4-(3-(2-chloro-5-fluoropyrimidin-4-yl)pyridin-2-yloxy)phenyl)-4-phenylphthalazin-1-amine (1.27 mg, 2.43 mmol), tert-butyl carbamate (712 mg, 6.08 mmol), potassium carbonate (10.1 g, 72.9 mmol), and 1,4-dioxane (12.2 ml, 2.43 mmol) were added. Then Pd(OAc)2/Xantphos solution was added via a syringe. The resulting mixture was heated to 110° C. under argon with vigorous stirring. After 3.5 h, LCMS showed mainly product at 1.793 min as [M+H]+=602 and deBoc product at 1.602 min as [M+H]+=502. The reaction was cooled to RT, diluted with DCM, passed through a pad of celite and silica gel (1 cm thick each) with an aid of DCM and a bit of MeOH. The filtrate was concentrated to afford tert-Butyl 5-fluoro-4-(2-(4-(4-phenylphthalazin-1-ylamino)phenoxy)pyridin-3-yl)pyrimidin-2-ylcarbamate, which was carried on without further purification. MS Calcd for C34H28FN7O3: [M]+=601. Found: [M+1]+=602.

Workup

  1. customThe title compound was prepared
  2. customThe tube was purged with argon
  3. customIn a separate sealed tube
  4. waitAfter 3.5 h
  5. customat 1.793 min
  6. customat 1.602 min
  7. temperatureThe reaction was cooled to RT
  8. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-53aa02a00ff5414ebd9fbb5a318d7c03
Source dataset
uspto-grants-2016_01
Patent number
US09242961B2

Reaction notes

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