2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 59631368, compound

HRID 1431595Notes

Reaction equation

HRID 1431595 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([F:13])=[CH:9][C:10]=2[F:12])[N:5]=[C:4]([C:14]2[CH:15]=[N:16][CH:17]=[C:18]([CH3:20])[CH:19]=2)[C:3]=1[CH3:21].[O:22]1[CH2:27][CH2:26][N:25]([C:28]2[C:33]([NH2:34])=[CH:32][C:31]([N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)=[CH:30][N:29]=2)[CH2:24][CH2:23]1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.CC(C)([O-])C.[Na+]>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].C1(C)C=CC=CC=1>[O:22]1[CH2:27][CH2:26][N:25]([C:28]2[C:33]([NH:34][C:2]3[C:11]4[C:6](=[CH:7][C:8]([F:13])=[CH:9][C:10]=4[F:12])[N:5]=[C:4]([C:14]4[CH:15]=[N:16][CH:17]=[C:18]([CH3:20])[CH:19]=4)[C:3]=3[CH3:21])=[CH:32][C:31]([N:35]3[CH2:36][CH2:37][O:38][CH2:39][CH2:40]3)=[CH:30][N:29]=2)[CH2:24][CH2:23]1

Participants

7

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 596310462,5-Dimorpholinopyridin-3-amineHCID 59631296HCID 59631296, compound

Product 1

HCID 59631368HCID 59631368, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

A screw-cap vial was charged with 4-chloro-5,7-difluoro-3-methyl-2-(5-methylpyridin-3-yl)quinoline (50 mg, 0.16 mmol), 2,5-dimorpholinopyridin-3-amine (43.4 mg, 0.16 mmol), tris(dibenzylideneacetone)dipalladium (0) (15.0 mg, 0.016 mmol), XPhos (15.6 mg, 0.033 mmol), sodium tert-butoxide (47.3 mg, 0.49 mmol), and toluene (1.5 mL). The mixture was stirred at 105° C. for 2 h, then cond. The resulting residue was partitioned between DCM and water, and the organic layer was dried over magnesium sulfate and cond. The crude material was purified by recrystallization in MeOH, affording N-(2,5-dimorpholinopyridin-3-yl)-5,7-difluoro-3-methyl-2-(5-methylpyridin-3-yl)quinolin-4-amine. Mass Spectrum (ESI) m/e=533.0 (M+1). 1H NMR (400 MHz, chloroform-d) δ ppm 8.64 (1H, d, J=1.8 Hz), 8.57 (1H, d, J=1.6 Hz), 7.83 (1H, s), 7.78 (1H, br. s.), 7.67 (1H, d, J=2.5 Hz), 7.63 (1H, d, J=9.4 Hz), 6.98-7.09 (1H, m), 6.32-6.42 (1H, m), 3.91 (4H, br. s.), 3.77-3.86 (4H, m), 3.09-3.41 (4H, br. s.), 2.99-3.09 (4H, m), 2.48 (3H, s), 2.17 (3H, s).

Workup

  1. customThe resulting residue was partitioned between DCM and water
  2. dry with materialthe organic layer was dried over magnesium sulfate and cond
  3. customThe crude material was purified by recrystallization in MeOH

Sources & evidence

ORD record
ord-219d680581c6420fb5e4da2797a0924e
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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