Toluene → HCID 86598735, compound

HRID 1192397Notes

Reaction equation

HRID 1192397 reaction equation
C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.[C:47]([O:51][C:52]([N:54]1[CH2:59][CH2:58][N:57]([C:60]2[C:65]([CH:66]3[CH2:68][CH2:67]3)=[C:64](Cl)[N:63]=[CH:62][N:61]=2)[CH2:56][CH2:55]1)=[O:53])([CH3:50])([CH3:49])[CH3:48].[C:70](=[NH:83])([C:77]1[CH:82]=[CH:81][CH:80]=[CH:79][CH:78]=1)[C:71]1[CH:76]=[CH:75][CH:74]=[CH:73][CH:72]=1.C1(C)C=CC=CC=1>CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:47]([O:51][C:52]([N:54]1[CH2:59][CH2:58][N:57]([C:60]2[C:65]([CH:66]3[CH2:68][CH2:67]3)=[C:64]([N:83]=[C:70]([C:71]3[CH:76]=[CH:75][CH:74]=[CH:73][CH:72]=3)[C:77]3[CH:82]=[CH:81][CH:80]=[CH:79][CH:78]=3)[N:63]=[CH:62][N:61]=2)[CH2:56][CH2:55]1)=[O:53])([CH3:50])([CH3:49])[CH3:48]

Participants

7

Reactant 4

HCID 1140TolueneHCID 136809Benzophenone imineHCID 634876Binap, (A+-)-HCID 86598736HCID 86598736, compound

Product 1

HCID 86598735HCID 86598735, compoundYield 89.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
95 °C

Procedure

A round bottom flask was charged with Pd(OAc)2 (84 mg, 0.37 mmol) and rac-BINAP (234 mg, 0.37 mmol) and purged with N2. To the flask was added 4-(5-cyclopropyl-6-chloro-pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester (1.27 g, 3.75 mmol), benzophenone imine (815 mg, 4.50 mmol), NaOBut (793 mg, 8.25 mmol) and toluene (24 mL). The mixture was heated to 95° C. for 1 hour. After cooling to room temperature, the reaction was diluted with EtOAc, filtered through Celite, and concentrated. The crude product was purified by column chromatography (hexanes:EtOAc, 2:1) to give 4-[6-(Benzhydrylidene-amino)-5-cyclopropyl-pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (1.62 g, 89%) as a colorless oil. 1H NMR (CDCl3, 400 MHz) δ 8.38 (s, 1H), 7.41 (m, 10H), 3.40 (m, 4H), 3.32 (m, 4H), 1.46 (s, 9H), 0.93 (m, 1H), 0.86 (m, 2H), 0.59 (m, 2H). LCMS (APCI+) m/z 484 [M+H]+; Rt=3.94 min.

Workup

  1. custompurged with N2
  2. temperatureAfter cooling to room temperature
  3. filtrationfiltered through Celite
  4. concentrationconcentrated
  5. customThe crude product was purified by column chromatography (hexanes:EtOAc, 2:1)

Sources & evidence

ORD record
ord-eda47f1805624ae6bd3071d092ead285
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

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