2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 50908277, compound

HRID 1431533Notes

Reaction equation

HRID 1431533 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]=[N:69][C:70]([O:73][CH2:74][CH:75]3[CH2:77][CH2:76]3)=[CH:71][CH:72]=2)[C:56]=1[CH3:78].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]>[CH:75]1([CH2:74][O:73][C:70]2[N:69]=[CH:68][C:67]([C:57]3[C:56]([CH3:78])=[C:55]([NH:47][C:46]4[C:41]([N:38]5[CH2:39][CH2:40][O:35][CH2:36][CH2:37]5)=[N:42][CH:43]=[C:44]([N:48]5[CH2:49][CH2:50][O:51][CH2:52][CH2:53]5)[CH:45]=4)[C:64]4[C:59](=[CH:60][C:61]([F:66])=[CH:62][C:63]=4[F:65])[N:58]=3)=[CH:72][CH:71]=2)[CH2:76][CH2:77]1

Participants

7

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 596310462,5-Dimorpholinopyridin-3-amineHCID 59631339HCID 59631339, compound

Product 1

HCID 50908277HCID 50908277, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

The Buchwald coupled product was prepared according to Procedure H using dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.021 g, 0.044 mmol), 2,5-dimorpholinopyridin-3-amine (0.088 g, 0.33 mmol), 4-chloro-2-(6-(cyclopropylmethoxy)pyridin-3-yl)-5,7-difluoro-3-methylquinoline (0.1 g, 0.28 mmol) and Pd2dba3 (0.010 g, 0.011 mmol) and sodium tert-butoxide (0.067 g, 0.70 mmol) in toluene (2.8 mL) at 100° C. for 1.6 h. The crude product was purified by column chromatography on silica gel (0 to 100% DCM/MeOH/ammonium hydroxide (90/9/1)) to give the desired product 2-(6-(cyclopropylmethoxy)-pyridin-3-yl)-N-(2,5-dimorpholinopyridin-3-yl)-5,7-difluoro-3-methylquinolin-4-amine. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.43 (1H, d, J=1.8 Hz), 8.00 (1H, dd, J=8.5, 2.4 Hz), 7.77 (1H, d, J=4.9 Hz), 7.63 (1H, dd, J=10.0, 1.6 Hz), 7.55 (1H, d, J=2.7 Hz), 7.41-7.49 (1H, m), 6.98 (1H, d, J=8.6 Hz), 6.43 (1H, d, J=2.7 Hz), 5.75 (1H, s), 4.18 (2H, d, J=7.2 Hz), 3.57-3.84 (8H, m), 3.15 (2H, br. s.), 2.99 (4H, m), 2.83 (2H, br. s.), 2.09 (3H, s), 1.23-1.34 (1H, m), 0.54-0.62 (2H, m), 0.33-0.41 (2H, m). Mass Spectrum (ESI) m/e=589.3 (M+1).

Workup

  1. customwas prepared
  2. customat 100° C.
  3. customfor 1.6 h
  4. customThe crude product was purified by column chromatography on silica gel (0 to 100% DCM/MeOH/ammonium hydroxide (90/9/1))

Sources & evidence

ORD record
ord-763c77fa324f4d9d975976039a8ccaba
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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