4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-propanenitrile → 3-(4-{2-[4-(1-Methyl-piperidin-4-yl)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-7-yl}-pyrazol-1-yl)-propionitrile

HRID 1262152

Reaction equation

HRID 1262152 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]([CH3:24])[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:33]2[CH:34]=[N:35][N:36]([CH2:38][CH2:39][C:40]#[N:41])[CH:37]=2)O1>>[CH3:24][N:21]1[CH2:20][CH2:19][CH:18]([C:15]2[CH:14]=[CH:13][C:12]([NH:11][C:8]3[N:7]=[CH:6][C:5]4=[CH:4][CH:3]=[C:2]([C:33]5[CH:34]=[N:35][N:36]([CH2:38][CH2:39][C:40]#[N:41])[CH:37]=5)[N:10]4[N:9]=3)=[CH:17][CH:16]=2)[CH2:23][CH2:22]1

Participants

3

Reactant 2

HCID 569657334-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-propanenitrileHCID 66711589HCID 66711589, compound

Product 1

HCID 667116823-(4-{2-[4-(1-Methyl-piperidin-4-yl)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-7-yl}-pyrazol-1-yl)-propionitrile

Procedure

(7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[4-(1-methyl-piperidin-4-yl)-phenyl]-amine (1.00E2 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 at 80° C. for 8 h. The reaction mixture was purified via ISCO silica gel chromatography using an amine capped column 50-100% EtOAc in hexanes (32 mg, 29%). LCMS=427.0 (M+H), HPLC rt=1.889 min, 96% purity. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.32 (s, 1H), 8.88 (s, 1H), 8.54 (s, 1H), 8.27 (s, 1H), 7.65 (d, J=7.6 Hz, 2H), 7.25 (d, J=8.5 Hz, 2H), 7.08 (d, J=4.3 Hz, 1H), 6.91 (d, J=4.7 Hz, 1H), 4.47 (t, J=6.4 Hz, 2H), 3.16 (t, J=6.5 Hz, 2H), 2.87 (d, J=10.8 Hz, 2H), 2.46-2.40 (m, 1H), 2.19 (s, 3H), 1.96 (t, J=10.8 Hz, 2H), 1.76-1.62 (m, 4H).

Workup

  1. customThe reaction mixture was purified via ISCO silica gel chromatography
  2. customcapped column 50-100% EtOAc in hexanes (32 mg, 29%)
  3. customLCMS=427.0 (M+H), HPLC rt=1.889 min, 96% purity

Sources & evidence

ORD record
ord-0a0878185c4c40d8b7c4f8a13275b812
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Linked notes

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