Trifluoroacetic acid → 2-[4-(4-{5-Hydroxy-7-[2-(methanesulfonyl-methyl-amino)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}-3-methoxy-phenyl)-piperidin-1-yl]-acetamide

HRID 1262337Notes

Reaction equation

HRID 1262337 reaction equation
[CH3:1][S:2]([N:5]([CH3:49])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C:12]1[N:20]2[C:15]([CH:16]=[N:17][C:18]([NH:21][C:22]3[CH:27]=[CH:26][C:25]([CH:28]4[CH2:33][CH2:32][N:31]([CH2:34][C:35]([NH2:37])=[O:36])[CH2:30][CH2:29]4)=[CH:24][C:23]=3[O:38][CH3:39])=[N:19]2)=[C:14]([O:40]COCC[Si](C)(C)C)[CH:13]=1)(=[O:4])=[O:3].FC(F)(F)C(O)=O>C(Cl)Cl>[OH:40][C:14]1[CH:13]=[C:12]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[N:5]([S:2]([CH3:1])(=[O:3])=[O:4])[CH3:49])[N:20]2[C:15]=1[CH:16]=[N:17][C:18]([NH:21][C:22]1[CH:27]=[CH:26][C:25]([CH:28]3[CH2:33][CH2:32][N:31]([CH2:34][C:35]([NH2:37])=[O:36])[CH2:30][CH2:29]3)=[CH:24][C:23]=1[O:38][CH3:39])=[N:19]2

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 667119472-(4-{4-[7-[2-(Methanesulfonyl-methyl-amino)-phenyl]-5-(2-trimethylsilanyl-ethoxymethoxy)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-3-methoxy-phenyl}-piperidin-1-yl)-acetamide

Product 1

HCID 1358738222-[4-(4-{5-Hydroxy-7-[2-(methanesulfonyl-methyl-amino)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}-3-methoxy-phenyl)-piperidin-1-yl]-acetamideYield 40.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Into a one dram vial, 2-(4-{4-[7-[2-(Methanesulfonyl-methyl-amino)-phenyl]-5-(2-trimethylsilanyl-ethoxymethoxy)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-3-methoxy-phenyl}-piperidin-1-yl)-acetamide (89 mg, 0.12 mmol), Methylene chloride (1.50 mL), and Trifluoroacetic Acid (0.50 mL, 6.5 mmol) was added. The reaction mixture was stirred at room temperature for 2 hours. The solvent was removed under vacuum. The reaction mixture was purified via HPLC reverse phase chromatography with 0.1% TFA in Water and 0.1% TFA in ACN. The collected fractions were lyophilized to give a yellow solid. The TFA salt was neutralized via a polymer sulfonic acid bound resin and washed with 2M NH3 in methanol. The solvent was removed to afford a yellow solid. The solid was triturated with Et2O to give 2-[4-(4-{5-Hydroxy-7-[2-(methanesulfonyl-methyl-amino)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}-3-methoxy-phenyl)-piperidin-1-yl]-acetamide as a yellow solid (28 mg, 32%). LCMS (E/I+) 580.15 (M+H). NMR 1H (DMSO-d6)-9.94 (s, 1H), 8.74 (s, 1H), 7.94-8.02 (m 1H), 7.88 (d, 1H, J=8.25 Hz), 7.59-7.67 (m, 1H), 7.48-7.56 (m, 2H), 7.40 (s, 1H), 7.21 (bs, 1H), 7.13 (bs, 1H), 6.85 (s, 1H), 6.67 (d, 1H, J=8.31 Hz), 6.35 (s, 1H), 3.83 (s, 3H), 3.05 (s, 3H), 2.77-2.99 (m, 7H), 2.32-2.45 (m, 1H), 2.06-2.23 (m, 2H), 1.60-1.87 (m, 4H).

Workup

  1. customThe solvent was removed under vacuum
  2. customThe reaction mixture was purified via HPLC reverse phase chromatography with 0.1% TFA in Water and 0.1% TFA in ACN
  3. customto give a yellow solid
  4. washwashed with 2M NH3 in methanol
  5. customThe solvent was removed
  6. customto afford a yellow solid
  7. customThe solid was triturated with Et2O

Sources & evidence

ORD record
ord-933896d6dcba4895958111d3e107ee66
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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