Potassium Phosphate, Tribasic → 2'-(3,3-Dimethylbut-1-enyl)-7'-(pyrimidin-5-yl)-5h-spiro[oxazole-4,9'-xanthen]-2-amine

HRID 335691Notes

Reaction equation

HRID 335691 reaction equation
Cl[C:2]1[CH:15]=[CH:14][C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8]([C:16]4[CH:17]=[N:18][CH:19]=[N:20][CH:21]=4)=[CH:9][CH:10]=3)[C:5]3([CH2:25][O:24][C:23]([NH2:26])=[N:22]3)[C:4]=2[CH:3]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[CH3:61][C:62]([CH3:69])([CH3:68])/[CH:63]=[CH:64]/B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(OCC)(=O)C.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].C1COCC1>[CH3:61][C:62]([CH3:69])([CH3:68])[CH:63]=[CH:64][C:2]1[CH:15]=[CH:14][C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8]([C:16]4[CH:17]=[N:18][CH:19]=[N:20][CH:21]=4)=[CH:9][CH:10]=3)[C:5]3([CH2:25][O:24][C:23]([NH2:26])=[N:22]3)[C:4]=2[CH:3]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 57067752-tert-Butyl-E-vinylboronic acidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 452561062'-Chloro-7'-(5-pyrimidinyl)spiro[1,3-oxazole-4,9'-xanthen]-2-amine

Product 1

HCID 672433762'-(3,3-Dimethylbut-1-enyl)-7'-(pyrimidin-5-yl)-5h-spiro[oxazole-4,9'-xanthen]-2-amineYield 64%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A microwave vial was charged with (rac)-2′-Chloro-7′-(5-pyrimidinyl)spiro[1,3-oxazole-4,9′-xanthen]-2-amine (90 mg, 247 μmol), Pd2 dba3 (11 mg, 12 μmol), X-Phos (12 mg, 25 μmol), (E)-3,3-dimethylbut-1-enylboronic acid (63 mg, 493 μmol) and potassium phosphate (157 mg, 740 μmol). THF (2 mL) was added and the mixture was heated at 120° C. in microwave reactor for 2 hrs. The mixture was diluted with ethyl acetate and filtered through plug of Celite. After removal of the solvents the residue was purified by flash chromatography on silica gel (12 g Redi-Sep column, 20-100% DCM/MeOH/NH4OH 90:10:1 in DCM) to give 2′-(3,3-dimethylbut-1-enyl)-7′-(pyrimidin-5-yl)-5H-spiro[oxazole-4,9′-xanthen]-2-amine (65 mg, 64% yield). This product was hydrogenated at 1 atm of H2 in MeOH/EtOAc mixture using 10% palladium on carbon (53 mg, 49 μmol) for 60 hrs. The reaction mixture was filtered and concentrated in vacuo and was further purified by reverse-phase HPLC (10-90% CH3CN/H2O with 0.1% TFA). The fractions containing product were combined and dried overnight under high vacuum to give 2′-(3,3-dimethylbutyl)-7′-(pyrimidin-5-yl)-5H-spiro[oxazole-4,9′-xanthen]-2-amine as its TFA salt.

Workup

  1. filtrationfiltered through plug of Celite
  2. customAfter removal of the solvents the residue
  3. customwas purified by flash chromatography on silica gel (12 g Redi-Sep column, 20-100% DCM/MeOH/NH4OH 90:10:1 in DCM)

Sources & evidence

ORD record
ord-d54b170b283a4516aa3ff5be7b721a34
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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