Triethylamine → HCID 70976546, compound

HRID 882241Notes

Reaction equation

[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10](Br)=[CH:11][CH:12]=2)[C@H:7]([NH:15][C:16]2[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][N:17]=2)[CH2:6][C@@H:5]1[CH3:24])(=[O:3])[CH3:2].[CH3:25][O:26][C:27]([C:29]1[N:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1)=[O:28].C(N(CC)CC)C>CO.COCCOC>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:32]3[CH:31]=[CH:30][C:29]([C:27]([O:26][CH3:25])=[O:28])=[N:34][CH:33]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:15][C:16]2[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][N:17]=2)[CH2:6][C@@H:5]1[CH3:24])(=[O:3])[CH3:2]

Participants

Conditions

Temperature: 120 °C

Procedure

6-(((2S,4R)-1-Acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile (for a preparation see Intermediate 2)(3.25 g, 8.44 mmol), {6-[(methyloxy)carbonyl]-3-pyridinyl}boronic acid (1.832 g, 10.12 mmol), {6-[(methyloxy)carbonyl]-3-pyridinyl}boronic acid (1.832 g, 10.12 mmol) and triethylamine (2.352 ml, 16.87 mmol) were combined in MeOH (30 ml) and DME (5 ml). The reaction mixture was divided between 2 vials and each heated at 120° C. for 45 min. The crude reaction mixtures were combined and concentrated in vacuo to give 4.4 g of crude brown solid. This was purified by chromatography on silica (100 g), eluting with over 1500 ml of EtOAc (compound leached off slowly) to give methyl 5-((2S,4R)-1-acetyl-4-((5-cyanopyridin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)picolinate (2.94 g, 6.66 mmol, 79% yield) as a brown foamy solid. LCMS (Formate, 2 min), Rt=0.81 min, MH+=442.

Workup

customThe crude reaction mixtures
concentrationconcentrated in vacuo
customto give 4.4 g of crude brown solid
customThis was purified by chromatography on silica (100 g)
washeluting with over 1500 ml of EtOAc (compound

Sources & evidence

ORD record: ord-48741a5487064c058831f9aae3b35864
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08993554B2

Reaction notes

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