1,2,3,4-Tetrahydroquinoline → HCID 59294537, compound

HRID 1877345Notes

Reaction equation

HRID 1877345 reaction equation
[F:1][C:2]([F:20])([F:19])[C:3]1[CH:4]=[C:5]([CH:16]=[CH:17][CH:18]=1)[O:6][C:7]1[N:15]=[CH:14][CH:13]=[CH:12][C:8]=1[C:9]([OH:11])=O.[NH:21]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH2:24][CH2:23][CH2:22]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>CN(C=O)C>[N:21]1([C:9]([C:8]2[C:7]([O:6][C:5]3[CH:16]=[CH:17][CH:18]=[C:3]([C:2]([F:1])([F:20])[F:19])[CH:4]=3)=[N:15][CH:14]=[CH:13][CH:12]=2)=[O:11])[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH2:24][CH2:23][CH2:22]1

Participants

6

Reactant 4

HCID 694601,2,3,4-TetrahydroquinolineHCID 81531DiisopropylethylamineHCID 2158912-(3-(Trifluoromethyl)phenoxy)-3-pyridinecarboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 59294537HCID 59294537, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-(3-trifluoromethyl-phenoxy)-nicotinic acid (200 mg, 0.71 mmol, 1.0 equiv) in anhydrous DMF (3 mL) was added 1,2,3,4-tetrahydro-quinoline (113 mg, 107 μL, 0.85 mmol, 1.2 equiv; [CAS RN 635-46-1]), N-ethyldiisopropylamine (457 mg, 617 μL, 3.53 mmol, 5.0 equiv; [CAS RN 7087-68-5]) and HATU (322 mg, 0.85 mmol, 1.2 equiv; [CAS RN 148893-10-1]). The reaction mixture was heated by microwave irradiation to 100° C. for 5 min. Removal of the solvent mixture under reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column equipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps, a Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water provided 157 mg (56%) of the title compound. MS (ISP): 399.2 [M+H]+.

Workup

  1. customRemoval of the solvent mixture
  2. customunder reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column
  3. customequipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps
  4. washa Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water

Sources & evidence

ORD record
ord-c4895d66e31e4ea58ff7b0350cb397f5
Source dataset
uspto-grants-2012_11
Patent number
US08309734B2

Reaction notes

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