2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → 4-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6-(4-morpholinyl)-3,4-dihydro-2H-1,4-benzoxazine

HRID 1618666Notes

Reaction equation

HRID 1618666 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([F:12])=[CH:9][CH:10]=2)[N:5]=[C:4]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)[C:3]=1[CH3:19].[O:20]1[CH2:25][CH2:24][N:23]([C:26]2[CH:35]=[CH:34][C:29]3[O:30][CH2:31][CH2:32][NH:33][C:28]=3[CH:27]=2)[CH2:22][CH2:21]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+]>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]>[F:12][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([N:33]3[C:28]4[CH:27]=[C:26]([N:23]5[CH2:24][CH2:25][O:20][CH2:21][CH2:22]5)[CH:35]=[CH:34][C:29]=4[O:30][CH2:31][CH2:32]3)=[C:3]([CH3:19])[C:4]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=3)=[N:5]2)=[CH:10][CH:9]=1

Participants

7

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 596310754-Chloro-7-fluoro-3-methyl-2-(pyridin-2-yl)quinolineHCID 67285003HCID 67285003, compound

Product 1

HCID 509393404-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6-(4-morpholinyl)-3,4-dihydro-2H-1,4-benzoxazine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

Prepared according to procedure Y by stirring 4-chloro-7-fluoro-3-methyl-2-(pyridin-2-yl)quinoline (50 mg, 0.183 mmol), 6-morpholino-3,4-dihydro-2H-benzo[b][1,4]oxazine (40.4 mg, 0.183 mmol), Pd2dba3 (16.8 mg, 0.018 mmol), XPhos (17.5 mg, 0.037 mmol) and sodium tert-butoxide (35.2 mg, 0.367 mmol) in toluene (2.0 mL) for 1 h at 120° C. in the microwave. Purification by reverse phase HPLC (10 to 60% acetonitrile in water) gave 4-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6-(4-morpholinyl)-3,4-dihydro-2H-1,4-benzoxazine). 1H NMR (400 MHz, chloroform-d) δ ppm 8.72-8.79 (1H, m), 7.81-7.96 (4H, m), 7.40 (1H, ddd, J=7.0, 5.0, 1.7 Hz), 7.28 (1H, ddd, J=9.2, 8.1, 2.6 Hz), 6.89 (1H, d, J=8.6 Hz), 6.29 (1H, dd, J=8.8, 2.7 Hz), 5.63 (1H, d, J=2.7 Hz), 4.40-4.51 (2H, m), 3.57-3.82 (6H, m), 2.71-2.82 (4H, m), 2.40 (3H, s). Mass Spectrum (ESI) m/e=457.0 (M+1).

Workup

  1. customPrepared
  2. customPurification by reverse phase HPLC (10 to 60% acetonitrile in water)

Sources & evidence

ORD record
ord-41512dbdf0a044fb96fa8c59b12c5b2a
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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