tert-Butanol → HCID 59427304, compound

HRID 1013677Notes

Reaction equation

HRID 1013677 reaction equation
CN(C1C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=CC=CC=1)C.CC(C)([O-])C.[Na+].Br[C:36]1[CH:45]=[C:44]2[C:39]([C:40]([O:46][C:47]3[CH:52]=[CH:51][C:50]([NH:53][C:54]4[C:63]5[C:58](=[CH:59][CH:60]=[CH:61][CH:62]=5)[C:57]([C:64]5[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=5)=[N:56][N:55]=4)=[CH:49][CH:48]=3)=[CH:41][CH:42]=[N:43]2)=[CH:38][CH:37]=1.[NH:70]1[CH2:75][CH2:74][O:73][CH2:72][CH2:71]1.O1CCOCC1.C(O)(C)(C)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(Cl)Cl>[O:73]1[CH2:74][CH2:75][N:70]([C:36]2[CH:45]=[C:44]3[C:39]([C:40]([O:46][C:47]4[CH:52]=[CH:51][C:50]([NH:53][C:54]5[C:63]6[C:58](=[CH:59][CH:60]=[CH:61][CH:62]=6)[C:57]([C:64]6[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=6)=[N:56][N:55]=5)=[CH:49][CH:48]=4)=[CH:41][CH:42]=[N:43]3)=[CH:38][CH:37]=2)[CH2:71][CH2:72]1

Participants

9

Reactant 6

HCID 6386tert-ButanolHCID 8083MorpholineHCID 312751,4-DioxaneHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl2×HCID 23676156Sodium t-butoxide2×HCID 67318235HCID 67318235, compound

Product 1

HCID 59427304HCID 59427304, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

The title compound was prepared according to a method described in Ali, M. H.; Buchwald, S. L. J. Org. Chem. 2001, 66, 2560. Pd2(dba)3(21 mg, 23 μmol), DavePhos (18 mg, 46 μmol), and sodium tert-butoxide (110 mg, 1141 μmol) were added into a screw-capped tube equipped with a stir bar. The tube was purged with argon. N-(4-(7-Bromoquinolin-4-yloxy)phenyl)-4-phenylphthalazin-1-amine (237 mg, 456 μmol) was added to the purged tube, followed by morpholine (159 μl, 1825 μmol), 1,4-dioxane (2074 μl, 456 μmol), and tert-butanol (1037 μl, 456 μmol). The tube was sealed and heated to 100° C. in an oil bath for 1 h. The reaction was cooled to rt, and 22 mg of Pd2(dba)3, 20 mg of DavePhos, and 80 mg of NaOt-Bu were added. The tube was resealed and placed in a preheated oil bath at 100° C. After another 3.5 h, LCMS showed mainly product at 1.434 min as [M+H]+=526. The mixture was passed through a pad of celite with an aid of CH2Cl2. The filtrate was concentrated. The product was purified by column chromatography on silica gel eluting with 70:30 to obtain top spot, then washing with 60:40 CH2Cl2:(90:10:1 CH2Cl2:MeOH:NOH) to collect the product. Fractions containing the product were concentrated. A yellow solid was obtained and dried in the vacuum oven. The yellow solid was further purified by RPLC on the acidic Gilson workstation. Fractions containing the product were diluted with CH2Cl2 and neutralized with sat. NaHCO3. The organic layer was separated, dried over MgSO4, filtered, and concentrated. Yellow solid was obtained. HPLC showed 100% pure. LCMS confirmed product. MS Calcd for C33H27N5O2: [M]+=525. Found: [M+H]+=526.

Workup

  1. customequipped with a stir bar
  2. customThe tube was purged with argon
  3. customThe tube was sealed
  4. temperatureThe reaction was cooled to rt
  5. customplaced in a preheated oil bath at 100° C
  6. customat 1.434 min
  7. concentrationThe filtrate was concentrated
  8. customThe product was purified by column chromatography on silica gel eluting with 70:30
  9. customto obtain top spot
  10. washwashing with 60:40 CH2Cl2
  11. custom(90:10:1 CH2Cl2:MeOH:NOH) to collect the product
  12. additionFractions containing the product
  13. concentrationwere concentrated
  14. customA yellow solid was obtained
  15. customdried in the vacuum oven
  16. customThe yellow solid was further purified by RPLC on the acidic Gilson workstation
  17. additionFractions containing the product
  18. additionwere diluted with CH2Cl2 and neutralized with sat. NaHCO3
  19. customThe organic layer was separated
  20. dry with materialdried over MgSO4
  21. filtrationfiltered
  22. concentrationconcentrated
  23. customYellow solid was obtained

Sources & evidence

ORD record
ord-b1cde4a5578047979a3a66b0ffce49b3
Source dataset
uspto-grants-2011_07
Patent number
US07981891B2

Reaction notes

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