Nitrogen → 1-(Cyclopropylmethyl)-5-[5-(2,4-difluorophenoxy)-2-methylsulfonylpyrimidin-4-yl]-3-methylpyridin-2-one

HRID 575724Notes

Reaction equation

HRID 575724 reaction equation
Cl[C:2]1[C:7]([O:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=2[F:16])=[CH:6][N:5]=[C:4]([S:17]([CH3:20])(=[O:19])=[O:18])[N:3]=1.[CH:21]1([CH2:24][N:25]2[CH:30]=[C:29](B3OC(C)(C)C(C)(C)O3)[CH:28]=[C:27]([CH3:40])[C:26]2=[O:41])[CH2:23][CH2:22]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].N#N>O1CCOCC1.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:21]1([CH2:24][N:25]2[CH:30]=[C:29]([C:2]3[C:7]([O:8][C:9]4[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=4[F:16])=[CH:6][N:5]=[C:4]([S:17]([CH3:20])(=[O:19])=[O:18])[N:3]=3)[CH:28]=[C:27]([CH3:40])[C:26]2=[O:41])[CH2:22][CH2:23]1

Participants

8

Reactant 4

HCID 947NitrogenHCID 62657Potassium Phosphate, TribasicHCID 1180215444-Chloro-5-(2,4-difluorophenoxy)-2-methylsulfonylpyrimidineHCID 1233814541-(Cyclopropylmethyl)-3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2(1H)-pyridinone

Product 1

HCID 1180220591-(Cyclopropylmethyl)-5-[5-(2,4-difluorophenoxy)-2-methylsulfonylpyrimidin-4-yl]-3-methylpyridin-2-oneYield 79.3%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
70 °C

Procedure

The title compound of Example 149, step 3 (200 mg, 0.62 mmol), the title compound of step 2 (250 mg, 0.69 mmol, 70% purity), Pd(dppf)Cl2 (88 mg, 0.12 mmol) and K3PO4 (3 M, 0.6 mL) in dioxane (6 mL) were purged with N2 and heated to 70° C. for 4 h. After silica gel chromatography (PE:EA=3:1˜1:1) the title compound (220 mg, yield: 78.8%) was obtained as a yellow solid. 1H NMR (CDCl3, 400 MHz) δ 7.45 (d, J=2.0 Hz, 1H), 8.25 (s, 1H), 8.16 (s, 1H), 7.24-7.22 (m, 1H), 7.12-7.10 (m, 1H), 7.10-7.03 (m, 1H), 3.92 (d, J=7.2 Hz, 2H), 3.38 (s, 3H), 2.26 (s, 3H), 1.27-1.21 (m, 1H), 0.65-0.60 (m, 2H), 0.42-0.38 (m, 2H). LCMS: 448.1 (M+H)+

Sources & evidence

ORD record
ord-a917a48a4401414f9138f61b42ebc0ea
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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