Tributylamine → [2-(3-Chloro-4-fluoro-phenoxy)-pyridin-3-yl]-(6,7-difluoro-3,4-dihydro-2H-quinolin-1-yl)-methanone

HRID 1877367Notes

Reaction equation

HRID 1877367 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][C:17]=1[F:18])[O:5][C:6]1[N:14]=[CH:13][CH:12]=[CH:11][C:7]=1[C:8]([OH:10])=O.[F:19][C:20]1[CH:21]=[C:22]2[C:27](=[CH:28][C:29]=1[F:30])[NH:26][CH2:25][CH2:24][CH2:23]2.C(N(CCCC)CCCC)CCC.[I-].ClC1C=CC=C[N+]=1C>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][C:17]=1[F:18])[O:5][C:6]1[C:7]([C:8]([N:26]2[C:27]3[C:22](=[CH:21][C:20]([F:19])=[C:29]([F:30])[CH:28]=3)[CH2:23][CH2:24][CH2:25]2)=[O:10])=[CH:11][CH:12]=[CH:13][N:14]=1

Participants

6

Reactant 4

HCID 7622TributylamineHCID 1670692-Chloro-1-methylpyridinium iodideHCID 128493372-(3-Chloro-4-fluoro-phenoxy)-nicotinic acidHCID 167848686,7-Difluoro-1,2,3,4-tetrahydroquinoline

Product 1

HCID 59294470[2-(3-Chloro-4-fluoro-phenoxy)-pyridin-3-yl]-(6,7-difluoro-3,4-dihydro-2H-quinolin-1-yl)-methanoneYield 9.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 2-(3-chloro-4-fluoro-phenoxy)-nicotinic acid (32.1 mg, 0.12 mmol, 1.0 equiv; Example 77, Step 1) in dichloromethane (1 mL) was added 6,7-difluoro-1,2,3,4-tetrahydro-quinoline (24.4 mg, 0.14 mmol, 1.2 equiv; [CAS RN 953717-64-1]), tri-n-butylamine (111.2 mg, 143 μL, 0.60 mmol, 5.0 equiv; [CAS RN 102-82-9]) and 2-chloro-1-methylpyridinium iodide (36.8 mg, 0.14 mmol, 1.2 equiv; [CAS RN 14338-32-0]). The reaction mixture was heated by microwave irradiation to 60° C. for 15 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 4.7 mg (9%) of the title compound. MS (ISP): 419.0 [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-8ad7e63897a3477a88bc63e84a9a5a06
Source dataset
uspto-grants-2012_11
Patent number
US08309734B2

Reaction notes

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