Binap, (A+-)- → 2-[6-((3R,6R)-5-{[Bis-(4-methoxy-phenyl)-phenyl-methyl]-amino}-3,6-dimethyl-6-trifluoromethyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-5-fluoro-pyridin-2-ylamino]-nicotinonitrile

HRID 925465Notes

Reaction equation

HRID 925465 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([NH:24][C:25]2[C@:26]([CH3:44])([C:40]([F:43])([F:42])[F:41])[O:27][CH2:28][C@:29]([C:32]3[C:37]([F:38])=[CH:36][CH:35]=[C:34](Br)[N:33]=3)([CH3:31])[N:30]=2)([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:5][CH:4]=1.[NH2:45][C:46]1[C:51]([C:52]#[N:53])=[CH:50][CH:49]=[CH:48][N:47]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.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]>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([NH:24][C:25]2[C@:26]([CH3:44])([C:40]([F:43])([F:42])[F:41])[O:27][CH2:28][C@:29]([C:32]3[N:33]=[C:34]([NH:45][C:46]4[N:47]=[CH:48][CH:49]=[CH:50][C:51]=4[C:52]#[N:53])[CH:35]=[CH:36][C:37]=3[F:38])([CH3:31])[N:30]=2)([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 634876Binap, (A+-)-HCID 8182592-Amino-3-cyanopyridineHCID 23676156Sodium t-butoxideHCID 89500352[Bis-(4-methoxy-phenyl)-phenyl-methyl]-[(2R,5R)-5-(6-bromo-3-fluoro-pyridin-2-yl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-amine

Product 1

HCID 903873312-[6-((3R,6R)-5-{[Bis-(4-methoxy-phenyl)-phenyl-methyl]-amino}-3,6-dimethyl-6-trifluoromethyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-5-fluoro-pyridin-2-ylamino]-nicotinonitrile

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of [bis-(4-methoxy-phenyl)-phenyl-methyl]-[(2R,5R)-5-(6-bromo-3-fluoro-pyridin-2-yl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-amine (250 mg, 0.372 mmol) in toluene (3.72 ml) was added 2-amino-3-pyridinecarbonitrile (221 mg, 1.859 mmol), Pd2(dba)3 (6.81 mg, 7.43 μmol), BINAP (9.26 mg, 0.015 mmol) and sodium tert-butoxide (50 mg, 0.520 mmol). The reaction mixture was degassed for 5 min and the microwave vial was sealed and stirred at 100° C. for 9 h. The reaction mixture was diluted with DCM and washed with water. The organic layer was dried with Na2SO4. The residue was purified by chromatography (silica gel; eluent DCM/MeOH+NH4OH) to afford the title compound.

Workup

  1. customThe reaction mixture was degassed for 5 min
  2. customthe microwave vial was sealed
  3. additionThe reaction mixture was diluted with DCM
  4. washwashed with water
  5. dry with materialThe organic layer was dried with Na2SO4
  6. customThe residue was purified by chromatography (silica gel; eluent DCM/MeOH+NH4OH)

Sources & evidence

ORD record
ord-df6dc3d85fc5496fb3e6c86391c95af7
Source dataset
uspto-grants-2016_03
Patent number
US09284284B2

Reaction notes

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