4-Fluorobenzylamine → 2-((R)-Indan-1-ylamino)-quinoline-6-carboxylic acid 4-fluoro-benzylamide

HRID 1931504Notes

Reaction equation

HRID 1931504 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH2:7])=[CH:4][CH:3]=1.C[Al](C)C.C([O:16][C:17]([C:19]1[CH:20]=[C:21]2[C:26](=[CH:27][CH:28]=1)[N:25]=[C:24]([NH:29][C@H:30]1[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[CH2:32][CH2:31]1)[CH:23]=[CH:22]2)=O)C.C(C(C(C([O-])=O)O)O)([O-])=O.[K+].[Na+]>O1CCOCC1.C1(C)C=CC=CC=1>[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH:7][C:17]([C:19]2[CH:20]=[C:21]3[C:26](=[CH:27][CH:28]=2)[N:25]=[C:24]([NH:29][C@H:30]2[C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[CH2:32][CH2:31]2)[CH:23]=[CH:22]3)=[O:16])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 673264-FluorobenzylamineHCID 9855836Potassium sodium tartarateHCID 16682925TrimethylaluminumHCID 68629716HCID 68629716, compound

Product 1

HCID 442187232-((R)-Indan-1-ylamino)-quinoline-6-carboxylic acid 4-fluoro-benzylamideYield 80%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent2×

Procedure

To a stirred solution of commercially available 4-fluoro-benzylamine (250 mg, 2.0 mmol) in dioxane (10 ml) was added drop wise at room temperature a 2M solution of trimethylaluminum in toluene (1 ml). The reaction mixture was allowed to stir for 1 h at room temperature, a solution of 2-((R)-indan-1-ylamino)-quinoline-6-carboxylic acid ethyl ester (166 mg, 0.5 mmol) in dioxane (4 ml) was added and the reaction mixture was heated for 2 h at 90° C. The reaction mixture was poured into 0.886M sodium-potassium-tartrate solution (25 ml) and extracted with ethyl acetate (2×40 ml). The combined organic layers were washed with brine (25 ml), dried (MgSO4) and evaporated. The crude product was purified by flash chromatography (ethyl acetate/heptane) on silica gel and crystallization (dichloromethane/MeOH/hexane) to yield the title compound as an off-white solid (164 mg, 80%), MS (ISP) 412.2 [(M+H)+]; m.p. 175° C.

Workup

  1. temperaturethe reaction mixture was heated for 2 h at 90° C
  2. extractionextracted with ethyl acetate (2×40 ml)
  3. washThe combined organic layers were washed with brine (25 ml)
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customThe crude product was purified by flash chromatography (ethyl acetate/heptane) on silica gel and crystallization (dichloromethane/MeOH/hexane)

Sources & evidence

ORD record
ord-5f75a54c35734792b19a454ed6677352
Source dataset
uspto-grants-2012_05
Patent number
US08188284B2

Reaction notes

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