Toluene → HCID 68764719, compound

HRID 529071Notes

Reaction equation

HRID 529071 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.Br[C:48]1[CH:49]=[C:50]2[C:56]3([CH2:61][CH2:60][N:59]([C:62]([O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:63])[CH2:58][CH2:57]3)[CH2:55][N:54]([C:69]3[C:70]4[C@H:77]([CH3:78])[CH2:76][CH2:75][C:71]=4[N:72]=[CH:73][N:74]=3)[C:51]2=[CH:52][CH:53]=1.[Cl:79][C:80]1[CH:81]=[C:82]([NH2:86])[CH:83]=[CH:84][CH:85]=1.C1(C)C=CC=CC=1>CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:79][C:80]1[CH:81]=[C:82]([NH:86][C:48]2[CH:49]=[C:50]3[C:56]4([CH2:61][CH2:60][N:59]([C:62]([O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:63])[CH2:58][CH2:57]4)[CH2:55][N:54]([C:69]4[C:70]5[C@H:77]([CH3:78])[CH2:76][CH2:75][C:71]=5[N:72]=[CH:73][N:74]=4)[C:51]3=[CH:52][CH:53]=2)[CH:83]=[CH:84][CH:85]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 79323-ChloroanilineHCID 634876Binap, (A+-)-HCID 68765224HCID 68765224, compound

Product 1

HCID 68764719HCID 68764719, compoundYield 59.5%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
95 °C

Procedure

A pear-shaped flask was charged with Pd(OAc)2 (0.9 mg, 0.004 mmol) and rac-BINAP (81 mg, 0.13 mmol) and purged with N2. To the flask was added (R)-tert-butyl 5-bromo-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-carboxylate (20 mg, 0.040 mmol), 3-chlorobenzenamine (10 mg, 0.080 mmol), NaOBut (7.7 mg, 0.080 mmol) and toluene (0.5 mL). The mixture was heated at about 95° C. for 2 days. After cooling to about room temperature, the reaction was diluted with EtOAc, filtered through Celite, and concentrated. The crude product was purified by column chromatography (DCM:MeOH, 80:1) to give (R)-tert-butyl 5-(3-chlorophenylamino)-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-carboxylate (13 mg, 59%) as a yellow oil. LCMS (APCI+) m/z 546 [M+H]+; Rt=4.24 min.

Workup

  1. custompurged with N2
  2. temperatureAfter cooling to about room temperature
  3. filtrationfiltered through Celite
  4. concentrationconcentrated
  5. customThe crude product was purified by column chromatography (DCM:MeOH, 80:1)

Sources & evidence

ORD record
ord-f1cabd6c6b354e0db98c456357128902
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

Loading…