Bromoacetonitrile → 6-(4-(1-(Cyanomethyl)piperidin-4-yl)phenylamino)-4-(2,3-difluorobenzylamino)nicotinamide

HRID 513275Notes

Reaction equation

HRID 513275 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.[CH3:33][CH2:34][N:35](C(C)C)C(C)C.BrCC#N>CN1C(=O)CCC1>[C:34]([CH2:33][N:25]1[CH2:24][CH2:23][CH:22]([C:19]2[CH:18]=[CH:17][C:16]([NH:15][C:8]3[CH:7]=[C:6]([NH:5][CH2:4][C:3]4[CH:28]=[CH:29][CH:30]=[C:31]([F:32])[C:2]=4[F:1])[C:11]([C:12]([NH2:14])=[O:13])=[CH:10][N:9]=3)=[CH:21][CH:20]=2)[CH2:27][CH2:26]1)#[N:35]

Participants

5

Reactant 3

HCID 11534BromoacetonitrileHCID 81531DiisopropylethylamineHCID 675004384-(2,3-Difluorobenzylamino)-6-(4-(piperidin-4-yl)phenylamino)nicotinamide

Product 1

HCID 866645436-(4-(1-(Cyanomethyl)piperidin-4-yl)phenylamino)-4-(2,3-difluorobenzylamino)nicotinamideYield 87.4%

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 bromoacetonitrile (36 μL, 0.54 mmol). The mixture was stirred at RT for 40 m and quenched with TFA. The mixture was subjected to reverse phase preparative HPLC to isolate the title compound (75 mg). MS found for C26H26F2N6O as (M+H)+ 477.4. UV: λ=256 nm. 1H NMR: (CD3OD) δ 8.17 (1H, s), 7.37 (2H, d, J=8.4 Hz), 7.25 (1H, m), 7.19-7.08 (4H, m), 5.82 (1H, s), 4.55 (2H, s), 4.43 (2H, s), 3.67 (2H, d, J=11.6 Hz), 3.23 (2H, t, J=12.0 Hz), 2.95 (1H, m), 2.19-2.03 (4H, m) ppm.

Workup

  1. customquenched with TFA

Sources & evidence

ORD record
ord-86ee4d6662e64e19a7fffc745f1fe748
Source dataset
uspto-grants-2015_08
Patent number
US09102625B2

Reaction notes

Loading…