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

HRID 1668930Notes

Reaction equation

HRID 1668930 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>[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[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 9832798Tris(dibenzylideneacetone) dipalladiumCatalyst

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 concentrated 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. concentrationThe DCM extracts were concentrated
  7. custompurified by flash chromatography (0-10% 2 M ammonia in methanol)

Sources & evidence

ORD record
ord-63984f37555c4f09bab36ba8a46eea78
Source dataset
uspto-grants-2011_08
Patent number
US07989461B2

Reaction notes

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