Cesium carbonate → Methyl-6-[2-(methylthio)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-6-yl]pyridine-2-carboxylate

HRID 338707Notes

Reaction equation

[CH3:1][S:2][C:3]1[N:4]=[CH:5][C:6]2[CH2:12][NH:11][CH2:10][CH2:9][C:7]=2[N:8]=1.[CH3:13][O:14][C:15](=[O:23])[C:16]1[CH:21]=[CH:20][CH:19]=[C:18](Br)[N:17]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:13][O:14][C:15]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([N:11]2[CH2:10][CH2:9][C:7]3[N:8]=[C:3]([S:2][CH3:1])[N:4]=[CH:5][C:6]=3[CH2:12]2)[N:17]=1)=[O:23]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 2-(methylthio)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (892 mg, 4.92 mmol), methyl-6-bromopicolinate (1.06 g, 4.92 mmol), Pd(OAc)2 (110 mg, 0.492 mmol), rac-BINAP (306 mg, 0.492 mmol), and Cs2CO3 (3.85 g, 11.81 mmol) in toluene (45 ml) was heated at 100° C. for 4.5 hours. The insolubles were filtered off and washed with ethyl acetate. The filtrate and washing were combined and concentrated. Elution through a flash column (silica gel 60, 230-400 mesh, 1:1 hexanes:EtOAc) gave the title compound as a viscous yellow oil which gradually solidified on standing (945 mg, 61%).

Workup

filtrationThe insolubles were filtered off
washwashed with ethyl acetate
washThe filtrate and washing
concentrationconcentrated
washElution through a flash column (silica gel 60, 230-400 mesh, 1:1 hexanes:EtOAc)

Sources & evidence

ORD record: ord-53e7e1a4b2124d3ea4446c1262ebfabd
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889870B2

Reaction notes

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