Ethanol → Ethyl 2-(2-aminoquinolin-6-yl)benzoate

HRID 930246Notes

Reaction equation

HRID 930246 reaction equation
[CH2:1]([O:3][C:4](=[O:20])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1B1OC(C)(C)C(C)(C)O1)[CH3:2].Br[C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][CH:31]=1)[N:28]=[C:27]([NH2:32])[CH:26]=[CH:25]2.C([O-])(=O)C.[K+].CCO.O>>[NH2:32][C:27]1[CH:26]=[CH:25][C:24]2[C:29](=[CH:30][CH:31]=[C:22]([C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=3[C:4]([O:3][CH2:1][CH3:2])=[O:20])[CH:23]=2)[N:28]=1

Participants

6

Reactant 5

HCID 702EthanolHCID 962WaterHCID 517044Potassium AcetateHCID 2773962Ethyl 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoateHCID 111836666-Bromoquinolin-2-amine

Product 1

HCID 66579382Ethyl 2-(2-aminoquinolin-6-yl)benzoate

Conditions

Temperature
85 °C

Procedure

To a microwave reaction vessel was added ethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (3.7 g, 13 mmol), 6-bromoquinolin-2-amine (2.0 g, 9.0 mmol), PdCl2(PPh(t-Bu)2)2 (0.084 g, 0.13 mmol), potassium acetate (1.8 g, 18 mmol), EtOH (9.9 ml, 170 mmol) and water (2.4 ml, 134 mmol). The reaction mixture was heated at 85° C. for 8 h, and was then partitioned between EtOAc and water. The organic layer was washed with water and brine and allowed to stand for 72 h. The supernatant was decanted from the resulting precipitate and the precipitate was dried in vacuo to give ethyl 2-(2-aminoquinolin-6-yl)benzoate. Step 2 6-(2-Ethoxyphenyl)quinolin-2-amine (1.0 g, 3.8 mmol) was taken up in THF and then 5N NaOH was added and the solution was stirred for 72 h. DCM was added and the solid was filtered to give ethyl 2-(2-aminoquinolin-6-yl)benzoate. Step 3 A solution of 2-(2-aminoquinolin-6-yl)benzoic acid (50 mg, 0.19 mmol), 4-fluoropiperidine (25 mg, 0.24 mmol), HATU (91 mg, 0.24 mmol), DIEA (100 uL, 0.57 mmol), and DMF (1 mL) was heated in a shaker oven at 60° C. for 1 h. The resulting solution was purified by HPLC (CH3CN/water modified with 0.1% TFA) to give (2-(2-aminoquinolin-6-yl)phenyl)(4-fluoropiperidin-1-yl)methanone. MS (ESI, pos. ion) m/z: 350 (M+1).

Workup

  1. customTo a microwave reaction vessel
  2. customwas then partitioned between EtOAc and water
  3. washThe organic layer was washed with water and brine
  4. customThe supernatant was decanted from the resulting precipitate
  5. customthe precipitate was dried in vacuo

Sources & evidence

ORD record
ord-3e93fdbc91174931aa6b538d0d7c009b
Source dataset
uspto-grants-2016_03
Patent number
US09296698B2

Reaction notes

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