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

HRID 513302

Reaction equation

HRID 513302 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.[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

Participants

9

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 4

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

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.

Workup

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

Sources & evidence

ORD record
ord-27fd9d58b687470db118f8f4ca850614
Source dataset
uspto-grants-2015_08
Patent number
US09102625B2

Linked notes

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