Hydrochloric Acid → 5-Chloro-N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-4-(1-methyl-1H-indol-3-yl)pyrimidin-2-amine HCl salt

HRID 1256049Notes

Reaction equation

HRID 1256049 reaction equation
FC(F)(F)CO.Cl.O1CCOCC1.[CH3:14][O:15][C:16]1[CH:22]=[C:21]([N:23]2[CH2:28][CH2:27][CH:26]([N:29]3[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]3)[CH2:25][CH2:24]2)[CH:20]=[CH:19][C:17]=1[NH2:18].[Cl:36][C:37]1[N:42]=[C:41]([C:43]2[C:51]3[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=3)[N:45]([CH3:52])[CH:44]=2)[C:40]([Cl:53])=[CH:39][N:38]=1>>[ClH:36].[Cl:53][C:40]1[C:41]([C:43]2[C:51]3[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=3)[N:45]([CH3:52])[CH:44]=2)=[N:42][C:37]([NH:18][C:17]2[CH:19]=[CH:20][C:21]([N:23]3[CH2:28][CH2:27][CH:26]([N:29]4[CH2:30][CH2:31][N:32]([CH3:35])[CH2:33][CH2:34]4)[CH2:25][CH2:24]3)=[CH:22][C:16]=2[O:15][CH3:14])=[N:38][CH:39]=1

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 64092,2,2-TrifluoroethanolHCID 312751,4-DioxaneHCID 457899912-Methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)anilineHCID 580714413-(2,5-Dichloropyrimidin-4-yl)-1-methyl-1H-indole2×

Product 1

HCID 667102435-Chloro-N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-4-(1-methyl-1H-indol-3-yl)pyrimidin-2-amine HCl saltYield 66.8%

Procedure

2,2,2-Trifluoroethanol (1.5 ml) was added to a 10 mL vial charged with 4 N HCl in dioxane (0.135 ml, 0.54 mmol), 2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)aniline (0.082 g, 0.27 mmol), and 3-(2,5-dichloropyrimidin-4-yl)-1-methyl-1H-indole (INTERMEDIATE 49, 0.075 g, 0.27 mmol). The reaction was stirred at RT for 5 min and then microwaved at 150° C. for 50 min. Concentration in vacuo gave a crude residue, and it was purified by silica gel chromatography (10% methanol andl% ammonium hydroxide in DCM) to give the product (0.105 g, 66.8%). The product was stirred in 20 mL of 0.5 N HCl in methanol for 1 min and then concentrated under reduced pressure to give the title product. (yellow solid).

Workup

  1. custommicrowaved at 150° C. for 50 min
  2. concentrationConcentration in vacuo
  3. customgave a crude residue, and it
  4. customwas purified by silica gel chromatography (10% methanol andl% ammonium hydroxide in DCM)

Sources & evidence

ORD record
ord-15bdfd8f6666478fbeab4fe8a4b3a922
Source dataset
uspto-grants-2013_06
Patent number
US08461170B2

Reaction notes

Loading…