Benzophenone imine → HCID 90025426, compound

HRID 920184Notes

Reaction equation

HRID 920184 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([C:32]2[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][CH:33]=2)([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[NH:10][C:11]2[CH2:12][S:13][CH2:14][C@:15]([C:18]3[CH:23]=[C:22](Br)[CH:21]=[CH:20][C:19]=3[F:25])([CH3:17])[N:16]=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:76](=[NH:89])([C:83]1[CH:88]=[CH:87][CH:86]=[CH:85][CH:84]=1)[C:77]1[CH:82]=[CH:81][CH:80]=[CH:79][CH:78]=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]>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([C:32]2[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][CH:33]=2)([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[NH:10][C:11]2[CH2:12][S:13][CH2:14][C@:15]([C:18]3[CH:23]=[C:22]([N:89]=[C:76]([C:77]4[CH:82]=[CH:81][CH:80]=[CH:79][CH:78]=4)[C:83]4[CH:88]=[CH:87][CH:86]=[CH:85][CH:84]=4)[CH:21]=[CH:20][C:19]=3[F:25])([CH3:17])[N:16]=2)=[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 90016427HCID 90016427, compound

Product 1

HCID 90025426HCID 90025426, compoundYield 81.7%

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

To a mixture of (R)—N-(bis(4-methoxyphenyl)(phenyl)methyl)-5-(5-bromo-2-fluorophenyl)-5-methyl-5,6-dihydro-2H-1,4-thiazin-3-amine (1.67 g, 2.76 mmol, Eq: 1.00), sodium tert-butoxide (795 mg, 8.27 mmol, Eq: 3), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (85.6 mg, 82.7 μmol, Eq: 0.03) and 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (117 mg, 276 μmol, Eq: 0.1) in toluene (22.0 ml) at 23° C. was added benzophenone imine (1.00 g, 926 μl, 5.52 mmol, Eq: 2) this reaction mixture was stirred under argon atmosphere at 105° C. for 5 hours. Extracted with water and ethyl acetate, dried the organic layer over Na2SO4, filtered off and evaporated totally. The crude material was purified by silica gel flash chromatography with n-heptane and ethyl acetate to give the (R)—N-(bis(4-methoxyphenyl)(phenyl)methyl)-5-(5-(diphenylmethyleneamino)-2-fluorophenyl)-5-methyl-5,6-dihydro-2H-1,4-thiazin-3-amine (1.59 g, 2.25 mmol, 81.7% yield) as a yellow oil. MS (ISP): m/z=706.3 [M+H]+.

Workup

  1. extractionExtracted with water and ethyl acetate
  2. dry with materialdried the organic layer over Na2SO4
  3. filtrationfiltered off
  4. customevaporated totally
  5. customThe crude material was purified by silica gel flash chromatography with n-heptane and ethyl acetate

Sources & evidence

ORD record
ord-1fe325f7655049fab6078647ac7ae970
Source dataset
uspto-grants-2016_03
Patent number
US09273042B2

Reaction notes

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