2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 50906985, compound

HRID 1431725Notes

Reaction equation

HRID 1431725 reaction equation
C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[O:35]1[CH2:40][CH2:39][N:38]([C:41]2[C:46]([NH2:47])=[CH:45][C:44]([N:48]3[CH2:53][CH2:52][O:51][CH2:50][CH2:49]3)=[CH:43][N:42]=2)[CH2:37][CH2:36]1.Cl[C:55]1[C:64]2[C:59](=[CH:60][C:61]([F:66])=[CH:62][C:63]=2[F:65])[N:58]=[C:57]([C:67]2[CH:68]=[CH:69][C:70]([N:73]3[CH2:77][CH2:76][CH:75]([OH:78])[CH2:74]3)=[N:71][CH:72]=2)[C:56]=1[CH3:79].CC(C)([O-])C.[Na+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[O:35]1[CH2:40][CH2:39][N:38]([C:41]2[C:46]([NH:47][C:55]3[C:64]4[C:59](=[CH:60][C:61]([F:66])=[CH:62][C:63]=4[F:65])[N:58]=[C:57]([C:67]4[CH:68]=[CH:69][C:70]([N:73]5[CH2:77][CH2:76][CH:75]([OH:78])[CH2:74]5)=[N:71][CH:72]=4)[C:56]=3[CH3:79])=[CH:45][C:44]([N:48]3[CH2:49][CH2:50][O:51][CH2:52][CH2:53]3)=[CH:43][N:42]=2)[CH2:37][CH2:36]1

Participants

7

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 596310462,5-Dimorpholinopyridin-3-amineHCID 59631169HCID 59631169, compound

Product 1

HCID 50906985HCID 50906985, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

The Buchwald coupled product was prepared according to Procedure S using of dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (8.73 mg, 0.018 mmol), 2,5-dimorpholinopyridin-3-amine (0.036 g, 0.14 mmol), 1-(5-(4-chloro-5,7-difluoro-3-methylquinolin-2-yl)pyridin-2-yl)pyrrolidin-3-ol (0.043 g, 0.11 mmol), Pd2dba3 (0.004 g, 0.005 mmol) and sodium tert-butoxide (0.027 g, 0.29 mmol) in toluene (1.1 mL) at 100° C. for 2.5 h. The crude product was purified by column chromatography on silica gel (0 to 100% DCM/methanol/ammonium hydroxide (90/9/1)) to give the desired product 1-(5-(4-(2,5-dimorpholinopyridin-3-ylamino)-5,7-difluoro-3-methylquinolin-2-yl)pyridin-2-yl)pyrrolidin-3-ol. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.43 (1H, d, J=2.2 Hz), 7.85 (1H, dd, J=8.8, 2.5 Hz), 7.74 (1H, d, J=6.1 Hz), 7.60 (1H, m), 7.56 (1H, d, J=2.5 Hz), 7.40 (1H, m), 6.58 (1H, d, J=9.2 Hz), 6.40 (1H, d, J=2.5 Hz), 5.00 (1H, m), 4.43 (1H, br. s.), 3.64-3.78 (8H, m), 3.55 (4H, m), 3.42 (4H, m), 3.00 (4H, d, J=4.9 Hz), 2.14 (3H, s), 1.95 (2H, br. s.). Mass Spectrum (ESI) m/e=604.3 (M+1).

Workup

  1. customwas prepared
  2. customThe crude product was purified by column chromatography on silica gel (0 to 100% DCM/methanol/ammonium hydroxide (90/9/1))

Sources & evidence

ORD record
ord-c0f88c60792f48dba4843c8e8d61b101
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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