2-Fluoroethyl bromide → 4-(2,3-Difluorobenzylamino)-6-(4-(1-(2-fluoroethyl)piperidin-4-yl)phenylamino)nicotinamide

HRID 513276Notes

Reaction equation

HRID 513276 reaction equation
[F:1][C:2]1[C:31]([F:32])=[CH:30][CH:29]=[CH:28][C:3]=1[CH2:4][NH:5][C:6]1[C:11]([C:12]([NH2:14])=[O:13])=[CH:10][N:9]=[C:8]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([CH:22]3[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)=[CH:18][CH:17]=2)[CH:7]=1.CCN(C(C)C)C(C)C.Br[CH2:43][CH2:44][F:45]>CN1C(=O)CCC1>[F:1][C:2]1[C:31]([F:32])=[CH:30][CH:29]=[CH:28][C:3]=1[CH2:4][NH:5][C:6]1[C:11]([C:12]([NH2:14])=[O:13])=[CH:10][N:9]=[C:8]([NH:15][C:16]2[CH:17]=[CH:18][C:19]([CH:22]3[CH2:23][CH2:24][N:25]([CH2:43][CH2:44][F:45])[CH2:26][CH2:27]3)=[CH:20][CH:21]=2)[CH:7]=1

Participants

5

Reactant 3

HCID 129822-Fluoroethyl bromideHCID 81531DiisopropylethylamineHCID 675004384-(2,3-Difluorobenzylamino)-6-(4-(piperidin-4-yl)phenylamino)nicotinamide

Product 1

HCID 866645444-(2,3-Difluorobenzylamino)-6-(4-(1-(2-fluoroethyl)piperidin-4-yl)phenylamino)nicotinamideYield 60.9%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Compound 4-(2,3-difluorobenzylamino)-6-(4-(piperidin-4-yl)phenylamino)nicotinamide (Example 209) (85 mg, 0.18 mmol) was dissolved in 3 mL NMP with DIEA (95 μL, 0.54 mmol). To it was added 1-bromo-2-fluoroethane (230 mg, 1.8 mmol). The mixture was stirred at RT for overnight. The reaction was about 70% completion. It was quenched with TFA and concentrated in vacuo. The mixture was subjected to reverse phase preparative HPLC to isolate the title compound (53 mg). MS found for C26H28F3N5O as (M+H)+ 484.4. UV: λ=256 nm. 1H NMR: (CD3OD) δ 8.19 (1H, s), 7.37 (2H, d, J=8.4 Hz), 7.25 (1H, m), 7.19-7.14 (3H, m), 7.10 (1H, m), 5.82 (1H, s), 4.97 (1H, m), 4.85 (1H, m), 4.55 (2H, s), 3.77 (2H, d, J=12.0 Hz), 3.62 (1H, m), 3.55 (1H, m), 3.28 (2H, m), 3.00 (1H, m), 2.15 (4H, m) ppm.

Workup

  1. customIt was quenched with TFA
  2. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-68e3dd6e6de148e0b1a7382b7377f890
Source dataset
uspto-grants-2015_08
Patent number
US09102625B2

Reaction notes

Loading…