Trifluoroacetic acid → 4-(2,3-Difluorobenzylamino)-6-(4-(1-formylpiperidin-4-yl)phenylamino)nicotinamide

HRID 513298Notes

Reaction equation

HRID 513298 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.[C:42](O)(C(F)(F)F)=[O:43]>CN(C=O)C>[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]([CH:42]=[O:43])[CH2:26][CH2:27]3)=[CH:20][CH:21]=2)[CH:7]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 675004384-(2,3-Difluorobenzylamino)-6-(4-(piperidin-4-yl)phenylamino)nicotinamide

Product 1

HCID 866645524-(2,3-Difluorobenzylamino)-6-(4-(1-formylpiperidin-4-yl)phenylamino)nicotinamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Compound 4-(2,3-difluorobenzylamino)-6-(4-(piperidin-4-yl)phenylamino)nicotinamide (Example 209) (70 mg, 0.15 mmol) was stirred in 4 mL DMF with DIEA (300 μL) at 120° C. in a sealed tube for two days. The mixture was acidified with 0.5 mL TFA and subjected to reverse phase preparative HPLC to isolate the title compound (41 mg). MS found for C25H25F2N5O2 as (M+H)+ 466.4. UV: λ=259 nm. 1H NMR: (CD3OD) δ 8.15 (1H, s), 8.06 (1H, s), 7.33 (2H, dt, J=8.8; 2.0 Hz), 7.28 (1H, m), 7.16 (1H, m), 7.13-7.07 (3H, m), 5.80 (1H, s), 4.56 (2H, s), 4.48 (1H, m), 3.86 (1H, m), 3.27 (1H, m), 2.93 (1H, m), 2.82 (1H, m), 1.94 (2H, m), 1.64 (2H, m) ppm.

Sources & evidence

ORD record
ord-9cca33dd29b44f64a379f5812b40cd60
Source dataset
uspto-grants-2015_08
Patent number
US09102625B2

Reaction notes

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