Hydrochloric Acid → HCID 178487094, compound

HRID 2383578Notes

Reaction equation

HRID 2383578 reaction equation
[CH3:1][N:2]([CH2:4][C:5]1[CH:42]=[CH:41][C:8]([CH:9]=[CH:10][C:11]2[C:19]3[C:14](=[CH:15][C:16]([CH:20]=[C:21]4[C:29]5[C:24](=[CH:25][CH:26]=[C:27]([O:30][CH3:31])[CH:28]=5)[NH:23][C:22]4=[O:32])=[CH:17][CH:18]=3)[N:13](COCC[Si](C)(C)C)[N:12]=2)=[CH:7][CH:6]=1)[CH3:3].B(F)(F)F.CCOCC.Cl>>[CH3:1][N:2]([CH2:4][C:5]1[CH:42]=[CH:41][C:8]([CH:9]=[CH:10][C:11]2[C:19]3[C:14](=[CH:15][C:16]([CH:20]=[C:21]4[C:29]5[C:24](=[CH:25][CH:26]=[C:27]([O:30][CH3:31])[CH:28]=5)[NH:23][C:22]4=[O:32])=[CH:17][CH:18]=3)[NH:13][N:12]=2)=[CH:7][CH:6]=1)[CH3:3]

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 8000Boron trifluoride etherateHCID 67445842HCID 67445842, compound

Product 1

HCID 178487094HCID 178487094, compound

Procedure

According to the method of Example A22B, 3-((3-(4-((dimethylamino)methyl) styryl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-6-yl)methylene)-5-methoxyindolin-2-one (19 mg, 0.033 mmol) was treated with boron trifluoride etherate, followed by 2 N HCl (water/EtOH) treatment. The solvents were removed in vacuo using additional EtOH to azeotropically remove water. The residue was dissolved in MeOH/EtOAc and filtered to remove solid, then the solvent was evaporated in vacuo. Purification by prep-HPLC gave the title compound (E isomer, first eluting fraction, 94% by HPLC) as an orange solid (11 mg, 60%). 1H NMR (400 MHz, CD3OD) δ ppm 8.26 (d, J=8.5 Hz, 1H), 7.88 (d, J=9.3 Hz, 2H), 7.80 (d, J=8.3 Hz, 2H), 7.61 (s, 2H), 7.51-7.58 (m, 3H), 7.26 (s, 1H), 6.84 (s, 2H), 4.34 (s, 2H), 3.63 (s, 3 H), 2.89 (s, 6H); MS ESI 451.2 [M+H]+, calcd for [C28H26N4O2+H]+ 451.22. The second eluting fraction was the Z-isomer (5 mg, 30%). 1H NMR (400 MHz, CD3OD) δ ppm 8.89 (s, 1H), 8.15 (d, J=9.0 Hz, 1H), 7.99 (dd, J=9.0, 1.3 Hz, 1H), 7.90 (s, 1H), 7.81 (d, J=8.3 Hz, 2H), 7.57-7.61 (m, 2H), 7.53 (d, J=8.3 Hz, 2H), 7.33 (d, J=2.0 Hz, 1H), 6.85 (dd, J=8.4, 2.4 Hz, 1H), 6.80 (d, J=8.4 Hz, 1H), 4.34 (s, 2H), 3.84 (s, 3H), 2.89 (s, 6H); MS ESI 451.2 [M+H]+, calcd for [C28H26N4O2+H]+ 451.22.

Workup

  1. customThe solvents were removed in vacuo
  2. dissolutionThe residue was dissolved in MeOH/EtOAc
  3. filtrationfiltered
  4. customto remove solid
  5. customthe solvent was evaporated in vacuo
  6. customPurification

Sources & evidence

ORD record
ord-80cdb2b170824ec0a7bc0f277b3ccd96
Source dataset
uspto-grants-2012_09
Patent number
US08263596B2

Reaction notes

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