Diisopropylethylamine → (R)-4-(2,3-difluorobenzylamino)-6-(4-(1-(1-methylpyrrolidine-2-carbonyl)piperidin-4-yl)phenylamino)nicotinamide

HRID 513306Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 513306
[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.O.[CH3:34][N:35]1[CH2:42][CH2:41][CH2:40][C@@H:36]1[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]([C@H:36]4[CH2:40][CH2:41][CH2:42][N:35]4[CH3:34])=[O:38])[CH2:26][CH2:27]3)=[CH:20][CH:21]=2)[CH:7]=1

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 56972828N-Methyl-D-proline monohydrateHCID 675004384-(2,3-Difluorobenzylamino)-6-(4-(piperidin-4-yl)phenylamino)nicotinamide

Produkt 1

HCID 67501023(R)-4-(2,3-difluorobenzylamino)-6-(4-(1-(1-methylpyrrolidine-2-carbonyl)piperidin-4-yl)phenylamino)nicotinamideAusbeute 53 %

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-methyl-D-proline monohydrate (33 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 (32 mg). MS found for C30H34F2N6O2 as (M+H)+ 549.5. UV: =259 nm. 1H NMR (a pair of rotomers): (CD3OD) δ 8.18 (1H, s), 7.32 (with 7.33, 2H, d, J=8.4 Hz), 7.25 (1H, m), 7.17 (1H, m), 7.13-7.07 (3H, m), 5.77 (with 5.79, 1H, s), 4.68 (2H, m), 4.57 (1H, m), 4.54 (2H, s), 3.90 (1H, m), 3.74 (1H, m), 3.27 (1H, m), 2.93 (with 2.97, 3H, s), 2.90 (2H, m), 2.68 (1H, m), 2.25 (1H, m), 2.11-1.95 (4H, m), 1.82-1.63 (2H, m) ppm.

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-45db8c417c6943c2be0c204bb94fb6c3
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09102625B2

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