N,N-Dimethylglycine hydrochloride → 4-(2,3-Difluorobenzylamino)-6-(4-(1-(2-(dimethylamino)acetyl)piperidin-4-yl)phenylamino)nicotinamide

HRID 513303Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 513303
[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.Cl.[CH3:34][N:35]([CH3:40])[CH2:36][C:37](O)=[O:38].CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>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]([C:37](=[O:38])[CH2:36][N:35]([CH3:40])[CH3:34])[CH2:26][CH2:27]3)=[CH:20][CH:21]=2)[CH:7]=1

Komponenten

6

Edukt 4

HCID 75605N,N-Dimethylglycine hydrochlorideHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 675004384-(2,3-Difluorobenzylamino)-6-(4-(piperidin-4-yl)phenylamino)nicotinamide

Produkt 1

HCID 675026674-(2,3-Difluorobenzylamino)-6-(4-(1-(2-(dimethylamino)acetyl)piperidin-4-yl)phenylamino)nicotinamideAusbeute 76,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Versuchsvorschrift

The mixture of compound 4-(2,3-difluorobenzylamino)-6-(4-(piperidin-4-yl)phenylamino)nicotinamide (Example 209) (50 mg, 0.11 mmol), N,N-dimethylglycine hydrochloride (31 mg, 0.22 mmol), DIEA (180 μL, 1.1 mmol) in 4 mL NMP was stirred at RT. To it was added BOP (210 mg, 0.55 mmol). The mixture was stirred for overnight, quenched with TFA, and subjected to reverse phase preparative HPLC to isolate the title compound (44 mg). MS found for C28H32F2N6O2 as (M+H)+ 523.5. UV: λ=259 nm. 1H NMR: (CD3OD) δ 8.17 (1H, s), 7.33 (2H, d, J=8.8 Hz), 7.26 (1H, m), 7.17 (1H, m), 7.14-7.07 (3H, m), 5.80 (1H, s), 4.68 (1H, m), 4.55 (2H, s), 4.37 (1H, d, J=16.0 Hz), 4.27 (1H, d, J=16.0 Hz), 3.81 (1H, m), 3.27 (1H, m), 2.97 (6H, s), 2.92-2.83 (2H, m), 1.95 (2H, m), 1.71 (2H, m) ppm.

Aufarbeitung

  1. stirringThe mixture was stirred for overnight
  2. customquenched with TFA

Quellen und Nachweise

ORD-Eintrag
ord-a4f7fe742d04418ca556ec0e13d556c1
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09102625B2

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