Diisopropylethylamine → HCID 66579127, compound

HRID 930248Notes

Reaction equation

HRID 930248 reaction equation
[NH2:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:12]3[CH:20]=[CH:19][CH:18]=[CH:17][C:13]=3[C:14](O)=[O:15])[CH:8]=2)[N:3]=1.[F:21][CH:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[NH2:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:12]3[CH:20]=[CH:19][CH:18]=[CH:17][C:13]=3[C:14]([N:25]3[CH2:26][CH2:27][CH:22]([F:21])[CH2:23][CH2:24]3)=[O:15])[CH:8]=2)[N:3]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27591594-FluoropiperidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66579296HCID 66579296, compound

Product 1

HCID 66579127HCID 66579127, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

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. customThe resulting solution was purified by HPLC (CH3CN/water modified with 0.1% TFA)

Sources & evidence

ORD record
ord-abbd7004713e4adc87961c5793024f9b
Source dataset
uspto-grants-2016_03
Patent number
US09296698B2

Reaction notes

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