Isopropanol → (S)-5-(3-(hydroxymethyl)pyrrolidin-1-yl)-3-methyl-7-(4-morpholinophenyl)pyrido[4,3-d]pyrimidin-4(3H)-one

HRID 1023306Notes

Reaction equation

Cl[C:2]1[N:11]=[C:10]([N:12]2[CH2:16][CH2:15][C@H:14]([CH2:17][OH:18])[CH2:13]2)[C:9]2[C:8](=[O:19])[N:7]([CH3:20])[CH:6]=[N:5][C:4]=2[CH:3]=1.CC1(C)C(C)(C)OB([C:29]2[CH:34]=[CH:33][C:32]([N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)=[CH:31][CH:30]=2)O1.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>[OH:18][CH2:17][C@H:14]1[CH2:15][CH2:16][N:12]([C:10]2[C:9]3[C:8](=[O:19])[N:7]([CH3:20])[CH:6]=[N:5][C:4]=3[CH:3]=[C:2]([C:29]3[CH:30]=[CH:31][C:32]([N:35]4[CH2:36][CH2:37][O:38][CH2:39][CH2:40]4)=[CH:33][CH:34]=3)[N:11]=2)[CH2:13]1

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of (S)-7-chloro-5-(3-(hydroxymethyl)pyrrolidin-1-yl)-3-methylpyrido[4,3-d]pyrimidin-4(3H)-one (26 mg, 0.088 mmol), 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)morpholine (28 mg, 0.097 mmol), Pd(PPh3)4 (10.2 mg, 0.0088 mmol), K2CO3 (36 mg, 0.26 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 (S)-5-(3-(hydroxymethyl)pyrrolidin-1-yl)-3-methyl-7-(4-morpholinophenyl)pyrido[4,3-d]pyrimidin-4(3H)-one as a slightly yellow solid. 1H NMR (CDCl3) δ (ppm) 8.06 (d, 2H), 8.01 (s, 1H), 7.19 (s, 1H), 6.96 (d, 2H), 3.91-3.81 (m, 5H), 3.78-3.65 (m, 4H), 3.65-3.58 (m, 1H), 3.50 (s, 3H), 3.27-3.24 (m, 4H), 2.57-2.47 (m, 1H), 2.15-2.07 (m, 1H), 1.90 (s, br, 1H), 1.82-1.72 (m, 1H); HPLC-MS calculated C23H27N5O3 (M+H+): 422.22, found: 422.20.

Workup

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

Sources & evidence

ORD record: ord-27e01b9da5254c50977b56a4deab81fa
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08722692B2

Reaction notes

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