Nitrogen → US10023592, Example 231

HRID 575700Notes

Reaction equation

HRID 575700 reaction equation
Br[C:2]1[C:7]2[N:8]=[CH:9][N:10]=[CH:11][C:6]=2[C:5](=[O:12])[N:4]([CH3:13])[CH:3]=1.[CH:14]1([CH2:17][O:18][C:19]2[CH:24]=[CH:23][C:22]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:21][C:20]=2B2OC(C)(C)C(C)(C)O2)[CH2:16][CH2:15]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].N#N>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CC(=O)OCC.C(Cl)Cl>[CH:14]1([CH2:17][O:18][C:19]2[CH:24]=[CH:23][C:22]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:21][C:20]=2[C:2]2[C:7]3[N:8]=[CH:9][N:10]=[CH:11][C:6]=3[C:5](=[O:12])[N:4]([CH3:13])[CH:3]=2)[CH2:15][CH2:16]1

Participants

10

Reactant 4

HCID 947NitrogenHCID 62657Potassium Phosphate, TribasicHCID 1180219268-Bromo-6-methylpyrido[4,3-d]pyrimidin-5(6H)-oneHCID 1234348592-[2-(Cyclopropylmethoxy)-5-(methylsulfonyl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 118022550US10023592, Example 231Yield 34.2%

Reagents, catalysts & solvents 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

The title compound of step 3 (100 mg, 0.42 mmol), the title compound of Example 90, step 1 (147 mg, 0.42 mmol), Pd(dppf)Cl2 (62 mg, 0.08 mmol), K3PO4 (221 mg, 1.04 mmol) in dioxane (4 mL) and H2O (0.5 mL) was purged with N2 and heated at 100° C. for 18 h. Following CH2Cl2 extractive work up, silica gel chromatography (PE:EA=2:10:1) and preparative HPLC, the title compound (54.57 mg, yield: 34.2%) was obtained as a yellow solid. 1H NMR: (DMSO-d6, 400 MHz) δ: 9.54 (s, 1H), 9.30 (s, 1H), 8.18 (s, 1H), 7.93 (dd, J1=8.8 Hz, J2=2.4 Hz, 1H), 7.85 (d, J=2.4 Hz, 1H), 7.31 (d, J=8.8 Hz, 1H), 3.91 (d, J=6.8 Hz, 2H), 3.61 (s, 3H), 3.20 (s, 3H), 0.94-0.92 (m, 1H), 0.35-0.30 (m, 2H), 0.10-0.06 (m, 2H). LCMS: 386.0 (M+H)+

Sources & evidence

ORD record
ord-a3dbcae969354f388b53186e7dd4aebb
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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