Dimethylformamide → 1-(4-(2-(5-amino-2-(furan-2-yl)-7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl)ethyl)piperazin-1-yl)-3-(2,4-difluorophenyl)propan-1-one

HRID 2239795Notes

Reaction equation

HRID 2239795 reaction equation
CS(OCC[N:8]1[C:16]2[N:15]=[C:14]([NH2:17])[N:13]3[N:18]=[C:19]([C:21]4[O:22][CH:23]=[CH:24][CH:25]=4)[N:20]=[C:12]3[C:11]=2[CH:10]=[CH:9]1)(=O)=O.Cl.[F:27][C:28]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=1[CH:35](N1CCNCC1)[C:36](=O)C.[CH3:45][CH2:46][N:47]([CH:51](C)C)[CH:48](C)C.[CH3:54][N:55]([CH:57]=[O:58])[CH3:56]>>[NH2:17][C:14]1[N:13]2[N:18]=[C:19]([C:21]3[O:22][CH:23]=[CH:24][CH:25]=3)[N:20]=[C:12]2[C:11]2[CH:10]=[CH:9][N:8]([CH2:45][CH2:46][N:47]3[CH2:51][CH2:56][N:55]([C:57](=[O:58])[CH2:36][CH2:35][C:29]4[CH:30]=[CH:31][C:32]([F:34])=[CH:33][C:28]=4[F:27])[CH2:54][CH2:48]3)[C:16]=2[N:15]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 68415544HCID 68415544, compoundHCID 866234642-{5-amino-2-(furan-2-yl)-7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl}ethyl methanesulfonate

Product 1

HCID 250201051-(4-(2-(5-amino-2-(furan-2-yl)-7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl)ethyl)piperazin-1-yl)-3-(2,4-difluorophenyl)propan-1-one

Conditions

Temperature
100 °C

Procedure

To a solution of the title D compound of Example 1, 2-{5-amino-2-(furan-2-yl)-7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl}ethyl methanesulfonate (0.06 g, 0.165 mmol) in dry DMF (5 mL), the title A compound, (2,4-difluorophenyl)piperazin-1-yl-propanone hydrochloride (0.33 mmol) and 0.06 mL of DIEA are added, and the solution is stirred at 100° C. for 5 h. The reaction mixture is cooled to RT, and the solvent is removed under reduced pressure. To the residue, acetonitrile is added and the solution is stirred at 60° C. for 0.5 h. The solution is then cooled to RT, and the resulting solids are collected by filtration to give 1-(4-(2-(5-amino-2-(furan-2-yl)-7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl)ethyl)piperazin-1-yl)-3-(2,4-difluorophenyl)propan-1-one: LC/MS (M+1=521.2). 1H NMR (DMSO-d6, 400 MHz), δ 2.40 (m, 4H), 2.58 (t, 2H, J=7.2 Hz), 2.68 (t, 2H, J=6.4 Hz), 2.79 (t, 2H, J=7.2 Hz), 3.37 (m, 2H), 3.41 (m, 2H), 4.25 (t, 2H, J=6.4 Hz), 6.59 (d, 1H, J=3.2 Hz), 6.71 (m, 1H), 6.99 (dt, 1H, J=8.4 Hz and 2.0 Hz), 7.15 (m, 2H), 7.18 (d, 1H, J=3.6 Hz), 7.36 (m, 1H), 7.49 (br s, 2H, NH2), 7.91 (s, 1H). Anal calculated for (C26H26F2N8O2+⅓ H2O): C, 59.31; H, 5.10; F, 7.22; N, 21.28; O, 7.09. Found C, 59.16; H, 481; N, 20.98.

Workup

  1. temperatureThe reaction mixture is cooled to RT
  2. customthe solvent is removed under reduced pressure
  3. additionTo the residue, acetonitrile is added
  4. stirringthe solution is stirred at 60° C. for 0.5 h
  5. temperatureThe solution is then cooled to RT
  6. filtrationthe resulting solids are collected by filtration

Sources & evidence

ORD record
ord-8cd7f6fb05e14bf1b33f1180ea684e72
Source dataset
uspto-grants-2010_05
Patent number
US07723343B2

Reaction notes

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