Cesium carbonate → 2-[2-Amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]-1,4-dihydroisoquinolin-3(2H)-one

HRID 2090308Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)[N:5]=[C:4]([NH2:15])[N:3]=1.[CH2:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH2:19][C:18](=[O:26])[NH:17]1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:15][C:4]1[N:3]=[C:2]([N:17]2[C:18](=[O:26])[CH2:19][C:20]3[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:16]2)[CH:7]=[C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)[N:5]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 4-chloro-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine (20 mg, 0.09 mmol, Example 1) and 1,4-dihydroisoquinolin-3(2H)-one (16 mg, 0.10 mmol, Tyger, Cat. No. D30080) in 1,4-dioxane (1 mL) was added (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (20 mg, 0.04 mmol, Aldrich, Cat. No. 526460), palladium acetate (4 mg, 0.02 mmol, Aldrich, Cat. No. 205869) and cesium carbonate (60 mg, 0.2 mmol, Aldrich, Cat. No. 202126). The mixture was degassed with nitrogen and heated at 100° C. 20 h. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in MeOH, and purified by RP-HPLC (pH=10 system) to afford the desired compound.

Workup

customThe mixture was degassed with nitrogen
custom20 h
concentrationThe reaction mixture was concentrated under reduced pressure
dissolutionThe residue was dissolved in MeOH
custompurified by RP-HPLC (pH=10 system)

Sources & evidence

ORD record: ord-c024a03cb2ca478fa921767ba32529d4
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08436008B2

Reaction notes

Loading…