2-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl → 6-methyl-5-(3-(6-(methylamino)pyrimidin-4-yl)pyridin-2-ylamino)isoquinolin-1(2H)-one

HRID 2092288Notes

Reaction equation

HRID 2092288 reaction equation
Cl[C:2]1[C:7]([C:8]2[N:13]=[CH:12][N:11]=[C:10]([NH:14][CH3:15])[CH:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[NH2:16][C:17]1[C:26]([CH3:27])=[CH:25][CH:24]=[C:23]2[C:18]=1[CH:19]=[CH:20][NH:21][C:22]2=[O:28].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1>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]>[CH3:27][C:26]1[C:17]([NH:16][C:2]2[C:7]([C:8]3[CH:9]=[C:10]([NH:14][CH3:15])[N:11]=[CH:12][N:13]=3)=[CH:6][CH:5]=[CH:4][N:3]=2)=[C:18]2[C:23](=[CH:24][CH:25]=1)[C:22](=[O:28])[NH:21][CH:20]=[CH:19]2

Participants

5

Reactant 3

HCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 529879275-amino-6-methylisoquinolin-1(2H)-oneHCID 589422526-(2-chloropyridin-3-yl)-N-methylpyrimidin-4-amine

Product 1

HCID 589422616-methyl-5-(3-(6-(methylamino)pyrimidin-4-yl)pyridin-2-ylamino)isoquinolin-1(2H)-oneYield 26%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
150 °C

Procedure

6-(2-chloropyridin-3-yl)-N-methylpyrimidin-4-amine (897 mg, 4.1 mmol), 5-amino-6-methylisoquinolin-1(2H)-one (779 mg, 4.5 mmol), 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (128 mg, 0.33 mmol) and tris(dibenzylideneacetone)dipalladium (0) (149 mg, 0.16 mmol) were added to a microwave tube. The tube was capped and flushed with nitrogen, and then lithium bis(trimethylsilyl)amide (16.9 mL, 1.0 M solution in THF) was added. The mixture was heated in a microwave reactor at 150° C. for 15 min. The reaction mixture was quenched with saturated aqueous sodium bicarbonate then extracted with DCM. The DCM extracts were conccentrated and purified by flash chromatography (0-10% 2 M ammonia in methanol) to give the title compound (380 mg, 26%). MS (M+H)+ 359.

Workup

  1. customThe tube was capped
  2. customflushed with nitrogen
  3. additionlithium bis(trimethylsilyl)amide (16.9 mL, 1.0 M solution in THF) was added
  4. customThe reaction mixture was quenched with saturated aqueous sodium bicarbonate
  5. extractionthen extracted with DCM
  6. custompurified by flash chromatography (0-10% 2 M ammonia in methanol)

Sources & evidence

ORD record
ord-6c7b68f8744d4843a6fcbd915f9705c2
Source dataset
uspto-grants-2013_05
Patent number
US08440674B2

Reaction notes

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