1-Methoxy-2-propanol → [1-[4-[[7-(2-Methoxyphenyl)pyrrolo[2,1-f][1,2,4]triazin-2-yl]amino]phenyl]piperidin-3-yl]-(4-methylpiperazin-1-yl)methanone;2,2,2-trifluoroacetic acid

HRID 1262037Notes

Reaction equation

HRID 1262037 reaction equation
CS(C1C=CC(C2N3C(C=NC(NC4C=CC(N5CCOCC5)=CC=4)=N3)=C(C)C=2)=CC=1)(=O)=O.[NH2:34][C:35]1[CH:40]=[CH:39][C:38]([N:41]2[CH2:46][CH2:45][CH2:44][CH:43]([C:47]([N:49]3[CH2:54][CH2:53][N:52]([CH3:55])[CH2:51][CH2:50]3)=[O:48])[CH2:42]2)=[CH:37][CH:36]=1.[F:56][C:57]([F:62])([F:61])[C:58]([OH:60])=[O:59].[CH3:63][O:64][C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][C:66]=1[C:71]1[N:79]2[C:74]([CH:75]=[N:76][C:77](NC3C=NC(N4CCOCC4)=CC=3)=[N:78]2)=[CH:73][CH:72]=1.COCC(O)C>CN1CCCC1=O>[F:56][C:57]([F:62])([F:61])[C:58]([OH:60])=[O:59].[CH3:63][O:64][C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][C:66]=1[C:71]1[N:79]2[C:74]([CH:75]=[N:76][C:77]([NH:34][C:35]3[CH:40]=[CH:39][C:38]([N:41]4[CH2:46][CH2:45][CH2:44][CH:43]([C:47]([N:49]5[CH2:54][CH2:53][N:52]([CH3:55])[CH2:51][CH2:50]5)=[O:48])[CH2:42]4)=[CH:37][CH:36]=3)=[N:78]2)=[CH:73][CH:72]=1

Participants

6

Reactant 4

HCID 79001-Methoxy-2-propanolHCID 66711307[7-(4-Methanesulfonyl-phenyl)-5-methyl-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-morpholin-4-yl-phenyl)-amineHCID 66711816[1-(4-Amino-phenyl)-piperidin-3-yl]-(4-methyl-piperazin-1-yl)-methanoneHCID 866616757-(2-methoxyphenyl)-N-(6-morpholin-4-yl-3-pyridinyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine;2,2,2-trifluoroacetic acid

Product 1

HCID 86661674[1-[4-[[7-(2-Methoxyphenyl)pyrrolo[2,1-f][1,2,4]triazin-2-yl]amino]phenyl]piperidin-3-yl]-(4-methylpiperazin-1-yl)methanone;2,2,2-trifluoroacetic acid

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

The titled compound (1-{4-[7-(2-Methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-3-yl)-(4-methyl-piperazin-1-yl)-methanone; compound with trifluoro-acetic acid was prepared in an analogous fashion to [7-(4-Methanesulfonyl-phenyl)-5-methyl-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(4-morpholin-4-yl-phenyl)-amine of Example 107 after: replacing 4-(4-morpholino)aniline with [1-(4-Amino-phenyl)-piperidin-3-yl]-(4-methyl-piperazin-1-yl)-methanone, replacing 2-Methanesulfinyl-7-(4-methanesulfonyl-phenyl)-5-methyl-pyrrolo[2,1-f][1,2,4]triazine with 2-Methanesulfinyl-7-(2-methoxy-phenyl)-5-methyl-pyrrolo[2,1-f][1,2,4]triazine (of Example 47), and replacing the solvent N-Methylpyrrolidinone with 1-Methoxy-2-propanol, to give after purification via reverse phase HPLC (1-{4-[7-(2-Methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-3-yl)-(4-methyl-piperazin-1-yl)-methanone; compound with trifluoro-acetic acid as a brown lyophylate (29 mg, 22%). LC/MS (E/I+) 526.22 (M+H). NMR 1H (DMSO-d6)-10.01 (bs, 1H), 9.45 (bs, 1H), 8.96 (s, 1H), 7.81-7.79 (m, 1H), 7.72-7.69 (d, 2H, J=8.58 Hz), 7.50-7.46 (m, 1H), 7.23-7.11 (m, 4H), 6.96-6.93 (m, 2H), 4.46-4.19 (bm, TFA salt and water provided poor resolution), 3.81 (s, 3H), 3.58-2.93 (bm; smeared as TFA salt), 2.83 (s, 3H), 1.86 (bs, 3H), 1.75 (bs, 1H).

Workup

  1. customto give
  2. customafter purification via reverse phase HPLC (1-{4-[7-(2-Methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-3-yl)-(4-methyl-piperazin-1-yl)-methanone; compound with trifluoro-acetic acid as a brown lyophylate (29 mg, 22%)

Sources & evidence

ORD record
ord-c13b9aaa684b420c8c16d82b5d8c34f1
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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