Trichloroacetonitrile → 6-((6-Chloro-8-fluoro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)-3-methoxyquinoline

HRID 2176701Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:4]=[N:5][C:6]2[C:11]([CH:12]=1)=[CH:10][C:9]([CH2:13][C:14](O)=O)=[CH:8][CH:7]=2.[Cl:17][C:18]1[CH:19]=[C:20]([F:26])[C:21]([NH:24][NH2:25])=[N:22][CH:23]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCN(C(C)C)C(C)C.ClC(Cl)(Cl)C#N>C(Cl)Cl>[Cl:17][C:18]1[CH:19]=[C:20]([F:26])[C:21]2[N:22]([C:14]([CH2:13][C:9]3[CH:10]=[C:11]4[C:6](=[CH:7][CH:8]=3)[N:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:12]4)=[N:25][N:24]=2)[CH:23]=1

Participants

Conditions

Temperature: 150 °C

Procedure

To a mixture of 2-(3-methoxyquinolin-6-yl)acetic acid (0.22 g, 1.0 mmol), 1-(5-chloro-3-fluoropyridin-2-yl)hydrazine (0.11 g, 0.68 mmol) and triphenylphosphine (0.97 g, 2.0 mmol) (on solid support) in DCM (5 mL) was added DIEA (0.24 ml, 1.4 mmol) followed by 2,2,2-trichloroacetonitrile (0.14 ml, 1.4 mmol) via a syringe. The mixture was then heated to 150° C. for 15 minutes in an appropriately sealed vial. The mixture was filtered and the filtrate was diluted with 50 mL of EtOAc. The solution was washed with 30 mL of satd. NaHCO3 followed by 30 mL of brine, dried over Na2SO4 and concentrated in vacuo. The crude product was purified by a silica gel column chromatography (EtOAc to 10% MeOH/EtOAc) to give light yellow solid as desired product. MS (ESI pos. ion) m/z: 343 (MH+). Calc'd exact mass for C11H12ClFN4O: 342.

Workup

filtrationThe mixture was filtered
additionthe filtrate was diluted with 50 mL of EtOAc
washThe solution was washed with 30 mL of satd
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customThe crude product was purified by a silica gel column chromatography (EtOAc to 10% MeOH/EtOAc)

Sources & evidence

ORD record: ord-9cd2a0c5af0946c9a132b1c5d29a09b0
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09066954B2

Reaction notes

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