4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-propanenitrile → 2-[4-(4-{7-[1-(2-Cyano-ethyl)-1H-pyrazol-4-yl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}-phenyl)-piperidin-1-yl]-acetamide

HRID 1262153

Reaction equation

HRID 1262153 reaction equation
Br[C:2]1[N:10]2[C:5]([CH:6]=[N:7][C:8]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([CH:18]4[CH2:23][CH2:22][N:21]([CH2:24][C:25]([NH2:27])=[O:26])[CH2:20][CH2:19]4)=[CH:14][CH:13]=3)=[N:9]2)=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:36]2[CH:37]=[N:38][N:39]([CH2:41][CH2:42][C:43]#[N:44])[CH:40]=2)O1>>[C:43]([CH2:42][CH2:41][N:39]1[CH:40]=[C:36]([C:2]2[N:10]3[C:5]([CH:6]=[N:7][C:8]([NH:11][C:12]4[CH:13]=[CH:14][C:15]([CH:18]5[CH2:19][CH2:20][N:21]([CH2:24][C:25]([NH2:27])=[O:26])[CH2:22][CH2:23]5)=[CH:16][CH:17]=4)=[N:9]3)=[CH:4][CH:3]=2)[CH:37]=[N:38]1)#[N:44]

Participants

3

Reactant 2

HCID 569657334-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-propanenitrileHCID 667107962-{4-[4-(7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino)-phenyl]-piperidin-1-yl}-acetamide

Product 1

HCID 667121512-[4-(4-{7-[1-(2-Cyano-ethyl)-1H-pyrazol-4-yl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}-phenyl)-piperidin-1-yl]-acetamide

Procedure

2-{4-[4-(7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino)-phenyl]-piperidin-1-yl}-acetamide (111 mg, 0.259 mmol) and 3-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-pyrazol-1-yl]-propionitrile (128 mg, 0.518 mmol) were reacted in an analogous manner to Example 881A. The resulting crude product was purified by ISCO chromatography (amine capped silica gel) with a gradient of 50-100% EtOAc in hexanes-30% MeOH in EtOAc (41 mg, 34%). LCMS=470.0 (M+H), HPLC rt=1.825 min, 95% purity. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.32 (s, 1H), 8.89 (s, 1H), 8.54 (s, 1H), 8.28 (s, 1H), 7.66 (d, J=8.5 Hz, 2H), 7.26 (d, J=8.5 Hz, 2H), 7.22 (bs, 1H), 7.14 (bs, 1H), 7.07 (d, J=4.3 Hz, 1H), 6.91 (d, J=4.3 Hz, 1H), 4.48 (t, J=6.4 Hz, 2H), 3.16 (t, J=6.4 Hz, 2H), 2.92 (d, J=10.5 Hz, 2H), 2.88 (s, 2H), 2.47-2.44 (m, 1H), 2.18-2.13 (m, 2H), 1.76-1.74 (m, 4H).

Workup

  1. customThe resulting crude product was purified by ISCO chromatography (amine capped silica gel) with a gradient of 50-100% EtOAc in hexanes-30% MeOH in EtOAc (41 mg, 34%)
  2. customLCMS=470.0 (M+H), HPLC rt=1.825 min, 95% purity

Sources & evidence

ORD record
ord-e54dfa005f9d4836b7f6ea30f5888e83
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Linked notes

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