Cesium carbonate → 6-(5-isopropyl-2-methylphenyl)-4-methoxy-2-(5-methyl-1-tosyl-1H-indazol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

HRID 80797

Reaction equation

HRID 80797 reaction equation
[CH3:1][O:2][C:3]1[C:4]2[CH2:32][NH:31][CH2:30][CH2:29][C:5]=2[N:6]=[C:7]([C:9]2[C:17]([CH3:18])=[CH:16][CH:15]=[C:14]3[C:10]=2[CH:11]=[N:12][N:13]3[S:19]([C:22]2[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=2)(=[O:21])=[O:20])[N:8]=1.FC(F)(F)S(O[C:39]1[CH:44]=[C:43]([CH:45]([CH3:47])[CH3:46])[CH:42]=[CH:41][C:40]=1[CH3:48])(=O)=O.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[Cs+].[Cs+]>C1COCC1.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]>[CH:45]([C:43]1[CH:42]=[CH:41][C:40]([CH3:48])=[C:39]([N:31]2[CH2:30][CH2:29][C:5]3[N:6]=[C:7]([C:9]4[C:17]([CH3:18])=[CH:16][CH:15]=[C:14]5[C:10]=4[CH:11]=[N:12][N:13]5[S:19]([C:22]4[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=4)(=[O:21])=[O:20])[N:8]=[C:3]([O:2][CH3:1])[C:4]=3[CH2:32]2)[CH:44]=1)([CH3:47])[CH3:46]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 130964092-Methyl-5-(propan-2-yl)phenyl trifluoromethanesulfonateHCID 712406574-methoxy-2-(5-methyl-1-tosyl-1H-indazol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Product 1

HCID 712404896-(5-isopropyl-2-methylphenyl)-4-methoxy-2-(5-methyl-1-tosyl-1H-indazol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 4-methoxy-2-(5-methyl-1-tosyl-1H-indazol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (250 mg, 0.556 mmol), 5-isopropyl-2-methylphenyl trifluoromethanesulfonate (235 mg, 0.834 mmol), X-Phos (53.0 mg, 0.111 mmol), Pd2(dba)3 (50.9 mg, 0.056 mmol), and Cs2CO3 (362 mg, 1.11 mmol) in THF (3 mL) was heated in a microwave reactor at 140° C. for 60 min. The reaction mixture was partitioned between EtOAc and water. The organic layer was washed with brine, dried (Na2SO4) and concentrated. The residue was purified by silica gel chromatography (0-50% EtOAc/heptane) to provide 6-(5-isopropyl-2-methylphenyl)-4-methoxy-2-(5-methyl-1-tosyl-1H-indazol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine. MS (ESI+) m/z 582.1 (M+H)+.

Workup

  1. customThe reaction mixture was partitioned between EtOAc and water
  2. washThe organic layer was washed with brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel chromatography (0-50% EtOAc/heptane)

Sources & evidence

ORD record
ord-454013d396d340aa937bb3762e16e56d
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Linked notes

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