1,2,3,4-Tetrahydroquinoline → (2-Chloro-5-fluoro-pyridin-3-yl)-(3,4-dihydro-2H-quinolin-1-yl)-methanone

HRID 1877350Notes

Reaction equation

[Cl:1][C:2]1[N:10]=[CH:9][C:8]([F:11])=[CH:7][C:3]=1[C:4]([OH:6])=O.[NH:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:15][CH2:14][CH2:13]1.C(N(C(C)C)C(C)C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C([O-])(O)=O.[Na+]>CN(C=O)C>[Cl:1][C:2]1[C:3]([C:4]([N:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:15][CH2:14][CH2:13]2)=[O:6])=[CH:7][C:8]([F:11])=[CH:9][N:10]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 2-chloro-5-fluoro-nicotinic acid (0.60 g, 3.42 mmol, 1.0 equiv; [CAS RN 38186-88-8]) in anhydrous DMF (5 mL) was added 1,2,3,4-tetrahydro-quinoline (0.55 g, 0.52 mL, 4.10 mmol, 1.2 equiv; [CAS RN 635-46-1]), N-ethyldiisopropylamine (2.21 g, 2.91 mL, 17.09 mmol, 5.0 equiv; [CAS RN 7087-68-5]) and HATU (1.56 g, 4.10 mmol, 1.2 equiv; [CAS RN 148893-10-1]). The reaction mixture was heated by microwave irradiation to 100° C. for 10 min. To the residue was added a sat. solution of NaHCO3 (50 mL) and the solution extracted with ethyl acetate (3×50 mL). The combined organic phases were dried over Na2SO4 and the product purified by silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane/ethyl acetate affording 0.51 g (52%) of the title compound as a light yellow solid. MS (ISP): 291.1 [M+H]+.

Workup

extractionthe solution extracted with ethyl acetate (3×50 mL)
dry with materialThe combined organic phases were dried over Na2SO4
customthe product purified by silica column chromatography
washeluting with a gradient of heptane/ethyl acetate affording 0.51 g (52%) of the title compound as a light yellow solid

Sources & evidence

ORD record: ord-acd46bce305849a0b8f40915d4468174
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08309734B2

Reaction notes

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