Diisopropylethylamine → 4-(2,3-Difluorobenzylamino)-6-(4-(1-(1,3-difluoropropan-2-yl)piperidin-4-yl)phenylamino)nicotinamide

HRID 513302

Reaktionsgleichung

Reaktionsgleichung von HRID 513302
[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.[F:42][CH2:43][C:44]([CH2:46][F:47])=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.O.CC(O)=O.O1CCOCC1>[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:44]([CH2:46][F:47])[CH2:43][F:42])[CH2:26][CH2:27]3)=[CH:20][CH:21]=2)[CH:7]=1

Komponenten

9

Edukt 4

HCID 81531DiisopropylethylamineHCID 2283971,3-DifluoroacetoneHCID 5049666Sodium triacetoxyborohydrideHCID 675004384-(2,3-Difluorobenzylamino)-6-(4-(piperidin-4-yl)phenylamino)nicotinamide

Produkt 1

HCID 675021984-(2,3-Difluorobenzylamino)-6-(4-(1-(1,3-difluoropropan-2-yl)piperidin-4-yl)phenylamino)nicotinamideAusbeute 9,2 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 111,2-DichloroethaneLösungsmittelHCID 176Acetic AcidLösungsmittelHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

Compound 4-(2,3-difluorobenzylamino)-6-(4-(piperidin-4-yl)phenylamino)nicotinamide (Example 209) (100 mg, 0.21 mmol) was stirred in 5 mL 1,2-dichloroethane and 5 mL dioxane as a slurry. To it were added DIEA (150 μL, 0.84 mmol) and then 1,3-difluoroacetone (100 mg, 1.05 mmol). The mixture was stirred at RT for 2 h. To the mixture were then added HOAc (200 μL) and NaBH(OAc)3 (222 mg, 1.05 mmol). The mixture was stirred at RT for overnight (incomplete reaction). To it was added water, and the mixture was concentrated in vacuo and subjected to reverse phase preparative HPLC to isolate the desired product (10 mg) and remaining starting compound. MS found for C27H29F4N5O as (M+H)+ 516.4. UV: λ=259 nm. 1H NMR: (CD3OD) δ 8.18 (1H, s), 7.38 (2H, d, J=8.0 Hz), 7.25 (1H, m), 7.19-7.09 (4H, m), 5.82 (1H, s), 5.15-4.90 (5H, m), 4.55 (2H, s), 3.77 (2H, m), 3.48 (2H, m), 3.03 (1H, m), 2.18 (4H, m) ppm.

Aufarbeitung

  1. stirringThe mixture was stirred at RT for overnight
  2. custom(incomplete reaction)
  3. concentrationthe mixture was concentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-27fd9d58b687470db118f8f4ca850614
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09102625B2

Verknüpfte Notizen

Wird geladen…