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

HRID 1262040Notes

Reaction equation

HRID 1262040 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH3:8][O:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[C:16]1[N:24]2[C:19]([CH:20]=[N:21][C:22]([NH:25][C:26]3[CH:31]=[CH:30][C:29]([N:32]4[CH2:37][CH2:36][CH2:35][CH:34](C(N5CCN(C)CC5)=O)[CH2:33]4)=[CH:28][CH:27]=3)=[N:23]2)=[CH:18][CH:17]=1.NC1C=CC(N2CCC([C:60]([N:62]3[CH2:67][CH2:66][N:65]([CH3:68])[CH2:64][CH2:63]3)=[O:61])CC2)=CC=1>>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH3:8][O:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[C:16]1[N:24]2[C:19]([CH:20]=[N:21][C:22]([NH:25][C:26]3[CH:31]=[CH:30][C:29]([N:32]4[CH2:37][CH2:36][CH:35]([C:60]([N:62]5[CH2:67][CH2:66][N:65]([CH3:68])[CH2:64][CH2:63]5)=[O:61])[CH2:34][CH2:33]4)=[CH:28][CH:27]=3)=[N:23]2)=[CH:18][CH:17]=1

Participants

3

Reactant 2

HCID 39426387[1-(4-Amino-phenyl)-piperidin-4-yl]-(4-methyl-piperazin-1-yl)-methanoneHCID 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

Product 1

HCID 86661676[1-[4-[[7-(2-Methoxyphenyl)pyrrolo[2,1-f][1,2,4]triazin-2-yl]amino]phenyl]piperidin-4-yl]-(4-methylpiperazin-1-yl)methanone;2,2,2-trifluoroacetic acid

Procedure

The titled compound (1-{4-[7-(2-Methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-4-yl)-(4-methyl-piperazin-1-yl)-methanone; compound with trifluoro-acetic acid was prepared in an analogous fashion to (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 of Example 443c after replacing [1-(4-Amino-phenyl)-piperidin-3-yl]-(4-methyl-piperazin-1-yl)-methanone with [1-(4-Amino-phenyl)-piperidin-4-yl]-(4-methyl-piperazin-1-yl)-methanone, 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-4-yl)-(4-methyl-piperazin-1-yl)-methanone; compound with trifluoro-acetic acid as a brown lyophylate (38 mg, 42%). LC/MS (E/I+) 526.21 (M+H). NMR 1H (DMSO-d6)-10.0 (bs, 1H), 9.5 (bs, 1H), 8.97 (s, 1H), 7.81-7.74 (m, 3H), 7.50-7.11 (m, 5H), 6.97-6.93 (m, 2H), 4.2-3.85 (bm, TFA salt and water provided poor resolution), 3.81 (s, 3H), 3.62-2.85 (bm; smeared as TFA salt), 2.83 (s, 3H), 1.88 (bs, 4H).

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-4-yl)-(4-methyl-piperazin-1-yl)-methanone; compound with trifluoro-acetic acid as a brown lyophylate (38 mg, 42%)

Sources & evidence

ORD record
ord-e722807cc89149e59e6d925c692355f9
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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