Nitrogen → US10023592, Example 311

HRID 518369Notes

Reaction equation

HRID 518369 reaction equation
Cl[C:2]1[C:7]([O:8][CH2:9][CH:10]2[CH2:12][CH2:11]2)=[CH:6][N:5]=[C:4]([S:13]([CH3:16])(=[O:15])=[O:14])[N:3]=1.[CH3:17][N:18]1[CH:27]=[C:26](B2OC(C)(C)C(C)(C)O2)[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19]1=[O:37].[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>[CH:10]1([CH2:9][O:8][C:7]2[C:2]([C:26]3[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[C:19](=[O:37])[N:18]([CH3:17])[CH:27]=3)=[N:3][C:4]([S:13]([CH3:16])(=[O:15])=[O:14])=[N:5][CH:6]=2)[CH2:12][CH2:11]1

Participants

8

Reactant 4

HCID 947NitrogenHCID 62657Potassium Phosphate, TribasicHCID 1180224454-Chloro-5-(cyclopropylmethoxy)-2-methylsulfonylpyrimidineHCID 1238094992-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-1(2H)-one

Product 1

HCID 118021982US10023592, Example 311Yield 68.1%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

The title compound of step 4 (5.00 g, 19.08 mmol), the title compound of Example 89, step 1 (5.98 g, 20.99 mmol), K3PO4 (12.13 g, 57.24 mmol), and Pd(dppf)Cl2 (1.40 g, 1.91 mmol) in dioxane/H2O (50 mL/5 mL) were N2 purged and heated at 80° C. for 8 h. Silica gel chromatography (PE: EA=10/1-1/1) to gave the title compound (5.01 g, yield: 68%) as a yellow solid. 1H NMR (CDCl3, 400 MHz) δ8.53 (s, 2H), 7.67-7.63 (m, 2H), 7.57-7.52 (m, 2H), 4.06 (d, J=6.8 Hz, 2H), 3.71 (s, 3H), 3.37 (s, 3H), 1.17 (m, 1H), 0.61 (m, 2H), 0.30 (m, 2H). LCMS: 386.1 (M+1)+

Workup

  1. custompurged

Sources & evidence

ORD record
ord-8e91744af6d341bb992942eb39b16b06
Source dataset
uspto-grants-2015_08
Patent number
US09115114B2

Reaction notes

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