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

HRID 1023315Notes

Reaction equation

HRID 1023315 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.C[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+].[CH3:48][CH:49](O)[CH3:50]>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>[CH:49]([N:21]1[CH2:26][CH2:25][N:24]([C:27]2[CH:32]=[CH:31][C:30]([C:2]3[N:11]=[C:10]([NH:12][C@@H:13]4[CH2:17][CH2:16][O:15][CH2:14]4)[C:9]4[C:8](=[O:18])[N:7]([CH3:19])[CH:6]=[N:5][C:4]=4[CH:3]=3)=[CH:29][CH:28]=2)[CH2:23][CH2:22]1)([CH3:50])[CH3:48]

Participants

7

Reactant 4

HCID 3776IsopropanolHCID 11430Potassium CarbonateHCID 179989051-Methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazineHCID 86667979(R)-7-chloro-3-methyl-5-(tetrahydrofuran-3-ylamino)pyrido[4,3-d]pyrimidin-4(3H)-one

Product 1

HCID 66959481(R)-7-(4-(4-isopropylpiperazin-1-yl)phenyl)-3-methyl-5-(tetrahydrofuran-3-ylamino)pyrido[4,3-d]pyrimidin-4(3H)-one

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

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 (15 mg, 0.053 mmol), 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine (19.4 mg, 0.059 mmol), Pd(PPh3)4 (6.1 mg, 0.0053 mmol), K2CO3 (22 mg, 0.16 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 on slilica gel flash column chromatography (eluent: 0-10% methanol in dichloromethane) to afford (R)-7-(4-(4-isopropylpiperazin-1-yl)phenyl)-3-methyl-5-(tetrahydrofuran-3-ylamino)pyrido[4,3-d]pyrimidin-4(3H)-one as a slightly yellow solid. 1H NMR (CDCl3) δ (ppm) 8.80 (d, 1H), 8.04 (d, 2H), 8.00 (s, 1H), 7.10 (s, 1H), 6.98 (d, 2H), 4.92-4.84 (m, 1H), 4.22 (dd, 1H), 4.06-3.99 (m, 1H), 3.95-3.89 (m, 1H), 3.80 (dd, 1H), 3.51 (s, 3H), 3.34-3.31 (m, 4H), 3.77-3.68 (m, 5H), 2.46-2.36 (m, 1H), 2.06-1.96 (m, 1H), 1.10 (d, 6H); HPLC-MS calculated C25H32N6O2 (M+H+): 449.27, found: 449.20.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe residue was purified on slilica gel flash column chromatography (eluent: 0-10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-edb5a77941124746981a1870ca599064
Source dataset
uspto-grants-2014_05
Patent number
US08722692B2

Reaction notes

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