2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-5,7-difluoro-3-methyl-2-(5-(methylsulfonyl)-3-pyridinyl)quinoline

HRID 1618694Notes

Reaction equation

HRID 1618694 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]([S:20]([CH3:23])(=[O:22])=[O:21])[CH:19]=2)[C:3]=1[CH3:24].[CH3:25][C:26]1([CH3:41])[C:30]2=[N:31][CH:32]=[C:33]([N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)[CH:34]=[C:29]2[NH:28][CH2:27]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>[CH3:25][C:26]1([CH3:41])[C:30]2=[N:31][CH:32]=[C:33]([N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)[CH:34]=[C:29]2[N:28]([C:2]2[C:11]3[C:6](=[CH:7][C:8]([F:13])=[CH:9][C:10]=3[F:12])[N:5]=[C:4]([C:14]3[CH:15]=[N:16][CH:17]=[C:18]([S:20]([CH3:23])(=[O:22])=[O:21])[CH:19]=3)[C:3]=2[CH3:24])[CH2:27]1

Participants

7

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 672844994-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl)-morpholineHCID 672857114-Chloro-5,7-difluoro-3-methyl-2-(5-(methylsulfonyl)pyridin-3-yl)quinoline

Product 1

HCID 672850854-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-5,7-difluoro-3-methyl-2-(5-(methylsulfonyl)-3-pyridinyl)quinoline

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

Prepared according to procedure Y by stirring 4-chloro-5,7-difluoro-3-methyl-2-(5-(methylsulfonyl)pyridin-3-yl)quinoline (40 mg, 0.108 mmol), 4-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl)morpholine (25.3 mg, 0.108 mmol), Pd2dba3 (10.1 mg, 10.85 μmol), X-Phos (10.3 mg, 0.022 mmol), sodium tert-butoxide (31.3 mg, 0.325 mmol), and toluene (1.1 mL) at 105° C. for 30 min. Purification by reverse-phase HPLC (0-80% acetonitrile in water) gave 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-5,7-difluoro-3-methyl-2-(5-(methylsulfonyl)-3-pyridinyl)quinoline. 1H NMR (400 MHz, chloroform-d) δ ppm 9.28 (1H, d, J=2.2 Hz), 9.17-9.20 (1H, m), 8.56-8.59 (1H, m), 7.67-7.72 (1H, m), 7.58-7.61 (1H, m), 7.06-7.13 (1H, m), 5.79-5.82 (1H, m), 3.86-3.91 (1H, m), 3.74-3.81 (5H, m), 3.23 (3H, s), 3.02-3.08 (4H, m), 2.37-2.41 (3H, m), 1.65-1.74 (3H, m), 1.57-1.65 (3H, m). Mass Spectrum (ESI) m/e=566.2 (M+1).

Workup

  1. customPrepared
  2. customPurification by reverse-phase HPLC (0-80% acetonitrile in water)

Sources & evidence

ORD record
ord-05e1cb158a824bfca01857bfd857895a
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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