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

HRID 513302

반응식

HRID 513302 반응식
[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

참가 물질

9

반응물 4

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

생성물 1

HCID 675021984-(2,3-Difluorobenzylamino)-6-(4-(1-(1,3-difluoropropan-2-yl)piperidin-4-yl)phenylamino)nicotinamide수율 9.2%

시약·촉매·용매 4

HCID 111,2-Dichloroethane용매HCID 176Acetic Acid용매HCID 962Water용매HCID 312751,4-Dioxane용매

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-27fd9d58b687470db118f8f4ca850614
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09102625B2

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