Trifluoroacetic acid → HCID 66712439, compound

HRID 1262314Notes

Reaction equation

HRID 1262314 reaction equation
C(OC(=O)[NH:7][CH2:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([NH:24][C:25]3[N:30]=[CH:29][C:28]4=[CH:31][CH:32]=[C:33]([C:34]5[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=5[N:40]([S:42]([CH3:45])(=[O:44])=[O:43])[CH3:41])[N:27]4[N:26]=3)=[C:20]([O:46][CH3:47])[CH:19]=2)[CH2:13][CH2:12]1)=[O:10])(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[NH2:7][CH2:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([NH:24][C:25]3[N:30]=[CH:29][C:28]4=[CH:31][CH:32]=[C:33]([C:34]5[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=5[N:40]([CH3:41])[S:42]([CH3:45])(=[O:44])=[O:43])[N:27]4[N:26]=3)=[C:20]([O:46][CH3:47])[CH:19]=2)[CH2:13][CH2:12]1)=[O:10]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66712647HCID 66712647, compound

Product 1

HCID 66712439HCID 66712439, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Into an 8 dram vial, {2-[4-(4-{7-[2-(Methanesulfonyl-methyl-amino)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}-3-methoxy-benzyl)-piperazin-1-yl]-2-oxo-ethyl}-carbamic acid tert-butyl ester (78 mg, 0.11 mmol), Methylene chloride (2.00 mL), and Trifluoroacetic Acid (1.00 mL, 13.0 mmol) were added. The reaction was stirred at room temperature over the weekend. The reaction was partitioned with saturated NaHCO3 and DCM. The organic was separated, washed with Brine and dried over Na2SO4. The solid was filtered and washed with DCM. 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 solid was partitioned with saturated NaHCO3 and DCM. The organic was separated, washed with Brine and dried over Na2SO4. The solid was filtered and washed with DCM. The solvent was removed under vacuum. The collected fractions afforded N-[2-(2-{4-[4-(2-Amino-acetyl)-piperazin-1-ylmethyl]-2-methoxy-phenylamino}-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenyl]-N-methyl-methanesulfonamide as a yellow solid. LCMS (E/I+) 579.09 (M+H). NMR 1H (DMSO-d6)-8.96 (s, 1H), 7.93-7.99 (m, 1H), 7.90 (d, 1H, J=8.05 Hz), 7.72 (s, 1H), 7.63-7.73 (m, 1H), 7.52-7.58 (m, 2H), 7.00 (d, 1H, J=4.66 Hz), 6.93-6.98 (m, 2H), 6.74 (d, 1H, J=7.94 Hz), 3.84 (s, 3H), 3.35-3.46 (m, 8H), 3.05 (s, 3H), 2.88 (s, 3H), 2.32 (bs, 4H).

Workup

  1. customThe reaction was partitioned with saturated NaHCO3 and DCM
  2. customThe organic was separated
  3. washwashed with Brine
  4. dry with materialdried over Na2SO4
  5. filtrationThe solid was filtered
  6. washwashed with DCM
  7. customThe solvent was removed under vacuum
  8. customThe reaction mixture was purified via HPLC
  9. customto give a yellow solid The solid
  10. customwas partitioned with saturated NaHCO3 and DCM
  11. customThe organic was separated
  12. washwashed with Brine
  13. dry with materialdried over Na2SO4
  14. filtrationThe solid was filtered
  15. washwashed with DCM
  16. customThe solvent was removed under vacuum

Sources & evidence

ORD record
ord-9b4fa7de56c142f0a8a5f9f15aae779a
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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