Cesium carbonate → 2-methyl-1-(3-methylbutyl)-4-phenyl-7-{[1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl]amino}-1,4-dihydropyrido[3,4-b]pyrazin-3(2H)-one

HRID 530132Notes

Reaction equation

HRID 530132 reaction equation
Cl[C:2]1[N:24]=[CH:23][C:5]2[N:6]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:7](=[O:16])[CH:8]([CH3:15])[N:9]([CH2:10][CH2:11][CH:12]([CH3:14])[CH3:13])[C:4]=2[CH:3]=1.[NH2:25][C:26]1[CH:27]=[C:28]2[C:32](=[CH:33][CH:34]=1)[N:31]([CH:35]1[CH2:40][CH2:39][CH2:38][CH2:37][O:36]1)[N:30]=[CH:29]2.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.C([O-])([O-])=O.[Cs+].[Cs+]>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.[Pd]>[CH3:15][CH:8]1[C:7](=[O:16])[N:6]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:5]2[CH:23]=[N:24][C:2]([NH:25][C:26]3[CH:27]=[C:28]4[C:32](=[CH:33][CH:34]=3)[N:31]([CH:35]3[CH2:40][CH2:39][CH2:38][CH2:37][O:36]3)[N:30]=[CH:29]4)=[CH:3][C:4]=2[N:9]1[CH2:10][CH2:11][CH:12]([CH3:14])[CH3:13]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 229339271-(Oxan-2-yl)-1H-indazol-5-amineHCID 895704047-chloro-2-methyl-1-(3-methylbutyl)-4-phenyl-1,4-dihydropyrido[3,4-b]pyrazin-3(2H)-one

Product 1

HCID 895704012-methyl-1-(3-methylbutyl)-4-phenyl-7-{[1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl]amino}-1,4-dihydropyrido[3,4-b]pyrazin-3(2H)-oneYield 65%

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
95 °C

Procedure

To a stirred mixture of 7-chloro-2-methyl-1-(3-methylbutyl)-4-phenyl-1,4-dihydropyrido[3,4-b]pyrazin-3(2H)-one (25.00 mg, 0.073 mmol) and 5-amino-1-(tetrahydropyranyl)-1H-indazole (23 mg, 0.11 mmol) in toluene (2.00 mL) was added bis(dibenzylideneacetone)palladium (10.0 mg, 0.011 mmol), 2,2′-Bis-diphenylphosphanyl-[1,1′]binaphthalenyl (13.5 mg, 0.022 mmol) and Cs2CO3 (71 mg, 0.22 mmol). The resulting mixture was heated at 95° C. for 5 h. LC-MS indicated completion of reaction. The bulk of solvent was removed under reduced pressure to give a crude residue, which was purified by flash column chromatography on silica gel (eluent: 2% methanol in dichloromethane) to give the desired product: (Yield: 65%) MS(ES+): m/z 525.21 [MH+]. HPLC: tR=3.26 (ZQ3, Polar_5 min).

Workup

  1. customcompletion of reaction
  2. customThe bulk of solvent was removed under reduced pressure
  3. customto give a crude residue, which
  4. customwas purified by flash column chromatography on silica gel (eluent: 2% methanol in dichloromethane)

Sources & evidence

ORD record
ord-7d3368c040814c97865a61998e5dcc92
Source dataset
uspto-grants-2016_05
Patent number
US09351974B2

Reaction notes

Loading…