Benzophenone imine → HCID 86674111, compound

HRID 1525168Notes

Reaction equation

HRID 1525168 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([C:35]2[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=2)([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[NH:10][C:11]2[O:12][CH2:13][C:14]([F:28])([F:27])[C@:15]3([N:26]=2)[C:24]2[C:19](=[CH:20][CH:21]=[C:22](Br)[CH:23]=2)[S:18][CH2:17][CH2:16]3)=[CH:5][CH:4]=1.[C:43](=[NH:56])([C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1.CC(C)([O-])C.[Na+].C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C>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.C(Cl)(Cl)Cl.[Pd].[Pd]>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([C:35]2[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=2)([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[NH:10][C:11]2[O:12][CH2:13][C:14]([F:28])([F:27])[C@:15]3([N:26]=2)[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([N:56]=[C:43]([C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)[C:50]4[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=4)[CH:23]=2)[S:18][CH2:17][CH2:16]3)=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 136809Benzophenone imineHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 23676156Sodium t-butoxideHCID 71059700HCID 71059700, compound

Product 1

HCID 86674111HCID 86674111, compoundYield 67.4%

Reagents, catalysts & solvents 2

HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

In a dry tube under an atmosphere of argon to a solution of (R)—N-(bis(4-methoxyphenyl)(phenyl)methyl)-6′-bromo-5,5-difluoro-5,6-dihydrospiro[[1,3]oxazine-4,4′-thiochroman]-2-amine (789 mg, 1.21 mmol) in toluene (10 ml) were added consecutively benzophenone imine (439 mg, 2.42 mmol), sodium tert-butoxide (349 mg, 3.63 mmol), 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl {CAS[564483-19-8]} (51.4 mg, 121 μmol), and tris(dibenzylideneacetone)dipalladium(0) chloroform adduct {CAS[52522-40-4]} (37.6 mg, 36.3 μmol). The tube was sealed and the reaction mixture stirred at 110° C. for 15 hours. For the workup, the solvent was evaporated at reduced pressure and the residue purified by chromatography on silica gel using a gradient of heptane/ethyl acetate=0:100 to 70:30 as the eluent. The (R)—N2-(bis(4-methoxyphenyl)(phenyl)methyl)-N6′-(diphenylmethylene)-5,5-difluoro-5,6-dihydrospiro[[1,3]oxazine-4,4′-thiochroman]-2,6′-diamine (613 mg, 67% yield) was obtained as a yellow solid. MS (ISP): m/z=752.5 [M+H]+.

Workup

  1. customThe tube was sealed
  2. customFor the workup, the solvent was evaporated at reduced pressure
  3. customthe residue purified by chromatography on silica gel using a gradient of heptane/ethyl acetate=0:100 to 70:30 as the eluent

Sources & evidence

ORD record
ord-0eb11c58192d4611bc930c91119c1b99
Source dataset
uspto-grants-2015_07
Patent number
US09079919B2

Reaction notes

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