Potassium Phosphate, Tribasic → Methyl 2-chloro-6-[(methylsulfonyl)(propyl)amino]isonicotinate

HRID 1160182Notes

Reaction equation

Cl[C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([Cl:12])[N:11]=1)[C:5]([O:7][CH3:8])=[O:6].[CH2:13]([NH:16][S:17]([CH3:20])(=[O:19])=[O:18])[CH2:14][CH3:15].[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:12][C:10]1[CH:9]=[C:4]([CH:3]=[C:2]([N:16]([S:17]([CH3:20])(=[O:19])=[O:18])[CH2:13][CH2:14][CH3:15])[N:11]=1)[C:5]([O:7][CH3:8])=[O:6]

Participants

Conditions

Temperature: 100 °C

Procedure

A solution of methyl 2,6-dichloroisonicotinate (4.8 g, 23.3 mmol) and N-propylmethanesulfonamide (3.8 g, 28.0 mmol) in dioxane (190 mL) was degassed with argon. Potassium phosphate tribasic (6.9 g, 32.6 mmol), xantphos (810 mg, 1.40 mmol) and Pd2 dba3 (427 mg, 0.47 mmol) were added, and the reaction mixture was stirred at 100° C., sealed, for 16 h. The reaction mixture was filtered on cellite, concentrated in vacuo, and purified by flash chromatography (2×300 g silica gel, 0 to 35% EtOAc in hexane) to give methyl 2-chloro-6-[(methylsulfonyl)(propyl)amino]isonicotinate. 1H NMR (400 MHz, CD3OD) δ 7.87 (s, 1H), 7.72 (s, 1H), 3.97 (s, 3H), 3.91 (t, J=7.2 Hz, 2H), 3.14 (s, 3H), 1.68-1.52 (m, 2H), 0.94 (t, J=7.4 Hz, 3H).

Workup

customsealed, for 16 h
filtrationThe reaction mixture was filtered on cellite
concentrationconcentrated in vacuo
custompurified by flash chromatography (2×300 g silica gel, 0 to 35% EtOAc in hexane)

Sources & evidence

ORD record: ord-576a588c5d32405e9a444d5ebda2c62f
Source dataset: uspto-grants-2010_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07816378B2

Reaction notes

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