2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 67285557, compound

HRID 1618689Notes

Reaction equation

HRID 1618689 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]([F:20])[CH:19]=2)[C:3]=1[CH3:21].[CH3:22][C:23]1([CH3:38])[C:27]2=[N:28][CH:29]=[C:30]([N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)[CH:31]=[C:26]2[NH:25][CH2:24]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>[CH3:22][C:23]1([CH3:38])[C:27]2=[N:28][CH:29]=[C:30]([N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)[CH:31]=[C:26]2[N:25]([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]([F:20])[CH:19]=3)[C:3]=2[CH3:21])[CH2:24]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 67285562HCID 67285562, compound

Product 1

HCID 67285557HCID 67285557, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

Prepared according to procedure Y by stirring 4-chloro-5,7-difluoro-2-(5-fluoropyridin-3-yl)-3-methylquinoline (50 mg, 0.162 mmol), 4-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl)morpholine (37.8 mg, 0.162 mmol), Pd2dba3 (22.3 mg, 0.024 mmol), XPhos (23.2 mg, 0.049 mmol), sodium tert-butoxide (47 mg, 0.486 mmol), and toluene (1.6 mL) at 100° C. for 2 h. Purification by reverse-phase HPLC (0-70% 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-2-(5-fluoro-3-pyridinyl)-3-methylquinoline. 1H NMR (400 MHz, chloroform-d) δ ppm 8.69-8.76 (1H, m), 8.62 (1H, d, J=2.7 Hz), 7.74-7.80 (1H, m), 7.65-7.70 (1H, m), 7.59-7.62 (1H, m), 7.04 (1H, ddd, J=11.7, 8.9, 2.5 Hz), 5.75 (1H, d, J=2.3 Hz), 3.84-3.88 (1H, m), 3.70-3.81 (5H, m), 2.97-3.06 (4H, m), 2.36 (3H, s), 1.58 (3H, s), 1.47-1.55 (3H, m). Mass Spectrum (ESI) m/e=506.0 (M+1).

Workup

  1. customPrepared
  2. customPurification by reverse-phase HPLC (0-70% acetonitrile in water)

Sources & evidence

ORD record
ord-7aafc020f72148d19f27cf04e1bf1e7f
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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