Isopropanol → (R)-3-methyl-7-(4-(4-methylpiperazin-1-yl)phenyl)-5-(tetrahydrofuran-3-ylamino) pyrido[4,3-d]pyrimidin-4(3H)-one

HRID 1023304Notes

Reaction equation

Cl[C:2]1[N:11]=[C:10]([NH:12][C@@H:13]2[CH2:17][CH2:16][O:15][CH2:14]2)[C:9]2[C:8](=[O:18])[N:7]([CH3:19])[CH:6]=[N:5][C:4]=2[CH:3]=1.[CH3:20][N:21]1[CH2:26][CH2:25][N:24]([C:27]2[CH:32]=[CH:31][C:30](B3OC(C)(C)C(C)(C)O3)=[CH:29][CH:28]=2)[CH2:23][CH2:22]1.C([O-])([O-])=O.[K+].[K+].CC(O)C>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH3:19][N:7]1[C:8](=[O:18])[C:9]2[C:10]([NH:12][C@@H:13]3[CH2:17][CH2:16][O:15][CH2:14]3)=[N:11][C:2]([C:30]3[CH:29]=[CH:28][C:27]([N:24]4[CH2:25][CH2:26][N:21]([CH3:20])[CH2:22][CH2:23]4)=[CH:32][CH:31]=3)=[CH:3][C:4]=2[N:5]=[CH:6]1

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of (R)-7-chloro-3-methyl-5-(tetrahydrofuran-3-ylamino)pyrido[4,3-d]pyrimidin-4(3H)-one (16 mg, 0.057 mmol), 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine (19 mg, 0.063 mmol), Pd(PPh3)4 (6.6 mg, 0.0057 mmol), K2CO3 (24 mg, 0.17 mmol), 2-propanol (3 mL) and H2O (1 mL) was stirred at 90° C. overnight. The reaction mixture was cooled to room temperature and worked-up. The residue was purified using slilica gel flash column chromatography (eluent: 0-10% methanol in dichloromethane) to afford (R)-3-methyl-7-(4-(4-methylpiperazin-1-yl)phenyl)-5-(tetrahydrofuran-3-ylamino) pyrido[4,3-d]pyrimidin-4(3H)-one as a slightly yellow solid. HPLC-MS calculated C23H28N6O2(M+H+): 421.24, found: 421.20.

Workup

temperatureThe reaction mixture was cooled to room temperature
customThe residue was purified

Sources & evidence

ORD record: ord-5d063aea64874066be549becf7f5619b
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08722692B2

Reaction notes

Loading…