Benzophenone imine → HCID 86670223, compound

HRID 2178191Notes

Reaction equation

HRID 2178191 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([NH:24][C:25]2[CH2:26][S:27](=[O:44])(=[O:43])[CH2:28][CH2:29][C@:30]([C:35]3[CH:40]=[C:39](Br)[CH:38]=[CH:37][C:36]=3[F:42])([CH:32]([F:34])[F:33])[N:31]=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.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.[C:81](=[NH:94])([C:88]1[CH:93]=[CH:92][CH:91]=[CH:90][CH:89]=1)[C:82]1[CH:87]=[CH:86][CH:85]=[CH:84][CH:83]=1>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]>[C:81](=[N:94][C:39]1[CH:38]=[CH:37][C:36]([F:42])=[C:35]([C@:30]2([CH:32]([F:34])[F:33])[CH2:29][CH2:28][S:27](=[O:44])(=[O:43])[CH2:26][C:25]([NH:24][C:9]([C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=3)([C:6]3[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)=[N:31]2)[CH:40]=1)([C:88]1[CH:89]=[CH:90][CH:91]=[CH:92][CH:93]=1)[C:82]1[CH:87]=[CH:86][CH:85]=[CH:84][CH:83]=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 70654403HCID 70654403, compound

Product 1

HCID 86670223HCID 86670223, compoundYield 51%

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
105 °C

Procedure

In a tube under an atmosphere of argon a solution of [bis-(4-methoxy-phenyl)-phenyl-methyl]-[(S)-5-(5-bromo-2-fluoro-phenyl)-5-difluoromethyl-1,1-dioxo-2,5,6,7-tetrahydro-1H-1λ6-[1,4]thiazepin-3-yl]-amine (356 mg, 518 μmol) in toluene (5 ml) was treated successively with sodium tert-butoxide (149 mg, 1.55 mmol), 2-di-tertbutylphosphino-2′,4′,6′-triisopropylbiphenyl (33 mg, 77.7 μmol), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (26.8 mg, 26 μmol), and benzophenonimine (188 mg, 1.04 mmol). The tube was sealed and the mixture was heated at 105° C. under stirring for 4 hours. For the workup, the brown solution was extracted with ethyl acetate and water. The organic layer was washed with brine, dried over sodium sulfate and evaporated at reduced pressure. The crude product was purified by chromatography on silica gel using a gradient of heptane and ethyl acetate 100:0 to 50:50 as the eluent. The {(S)-5-[5-(benzhydrylidene-amino)-2-fluoro-phenyl]-5-difluoromethyl-1,1-dioxo-2,5,6,7-tetrahydro-1H-1λ6-[1,4]thiazepin-3-yl}-[bis-(4-methoxy-phenyl)-phenyl-methyl]-amine (207 mg, 51% yield) was obtained as a light yellow foam. MS (ISN): m/z=786.5 [M−H]−.

Workup

  1. customThe tube was sealed
  2. extractionFor the workup, the brown solution was extracted with ethyl acetate and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. customevaporated at reduced pressure
  6. customThe crude product was purified by chromatography on silica gel using a gradient of heptane and ethyl acetate 100:0 to 50:50 as the eluent

Sources & evidence

ORD record
ord-cdb048065d4b413396cbabbb1969ce58
Source dataset
uspto-grants-2015_06
Patent number
US09067924B2

Reaction notes

Loading…