Binap, (A+-)- → HCID 68780154, compound

HRID 2264460Notes

Reaction equation

HRID 2264460 reaction equation
Cl[C:2]1[N:11]=[C:10]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[C:9]2[C:4](=[CH:5][C:6]([O:20][CH3:21])=[C:7]([O:18][CH3:19])[CH:8]=2)[N:3]=1.[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][CH:32]([NH2:35])[CH2:31][CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O(C(C)(C)C)[K]>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]>[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][CH:32]([NH:35][C:2]2[N:11]=[C:10]([N:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)[C:9]3[C:4](=[CH:5][C:6]([O:20][CH3:21])=[C:7]([O:18][CH3:19])[CH:8]=3)[N:3]=2)[CH2:31][CH2:30]1)=[O:28])([CH3:25])([CH3:23])[CH3:24]

Participants

7

Reactant 4

HCID 634876Binap, (A+-)-HCID 12682914-Amino-1-Boc-piperidineHCID 17135262-chloro-6,7-dimethoxy-4-(4-morpholinyl)quinazolineHCID 178418922HCID 178418922, compound

Product 1

HCID 68780154HCID 68780154, compoundYield 52%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

A mixture of 2-chloro-6,7-dimethoxy-4-morpholin-4-yl-quinazoline (3.10 g, 10.01 mmol, 1.0 equiv; commercially available from Specs Research Laboratory, The Netherlands), 4-amino-piperidine-1-carboxylic acid tert-butyl ester (2.00 g, 10.01 mmol, 1.0 equiv; commercially available), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (0.25 g, 0.40 mmol, 0.04 equiv), tris(dibenzylideneacetone)dipalladium(0) (0.21 g, 0.20 mmol, 0.02 equiv) and KOtert-Bu (1.35 g, 12.01 mmol, 1.2 equiv) in toluene (10 mL) was heated under Ar by microwave irradiation to 100° C. for 2 h. The crude reaction mixture was filtered through Hyflo Super Cel, a sat. solution of sodium chloride (100 mL) was added and the mixture extracted with ethyl acetate (3×50 mL). The combined organic phases were concentrated by evaporation under reduced pressure and the residue purified by silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane (+1% triethylamine)/ethyl acetate to provide 2.45 g (52%) of the title compound. MS (ISP): 474.4 [M+H]+.

Workup

  1. customThe crude reaction mixture
  2. filtrationwas filtered through Hyflo Super Cel
  3. additiona sat. solution of sodium chloride (100 mL) was added
  4. extractionthe mixture extracted with ethyl acetate (3×50 mL)
  5. concentrationThe combined organic phases were concentrated by evaporation under reduced pressure
  6. customthe residue purified by silica column chromatography
  7. washeluting with a gradient of heptane (+1% triethylamine)/ethyl acetate

Sources & evidence

ORD record
ord-6cbee375fc6c46048a89055c7d38a155
Source dataset
uspto-grants-2010_12
Patent number
US07855194B2

Reaction notes

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