Boron trifluoride etherate → HCID 178517054, compound

HRID 1615274Notes

Reaction equation

HRID 1615274 reaction equation
[N:1]1[CH:6]=[CH:5][C:4](/[CH:7]=[CH:8]/[C:9]2[C:17]3[C:12](=[CH:13][C:14](/[CH:18]=[C:19]4/[C:20](=[O:28])[NH:21][C:22]5[C:27]/4=[CH:26][CH:25]=[CH:24][CH:23]=5)=[CH:15][CH:16]=3)[N:11](COCC[Si](C)(C)C)[N:10]=2)=[CH:3][CH:2]=1.B(F)(F)F.CCOCC.OCN1C2C(=CC=C(/C=C3/C(=O)NC4C/3=CC=CC=4)C=2)C(/C=C/C2C=CN=CC=2)=N1>C(Cl)Cl>[N:1]1[CH:6]=[CH:5][C:4](/[CH:7]=[CH:8]/[C:9]2[C:17]3[C:12](=[CH:13][C:14](/[CH:18]=[C:19]4/[C:20](=[O:28])[NH:21][C:22]5[C:27]/4=[CH:26][CH:25]=[CH:24][CH:23]=5)=[CH:15][CH:16]=3)[NH:11][N:10]=2)=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 8000Boron trifluoride etherateHCID 68755937HCID 68755937, compoundHCID 69811336HCID 69811336, compound

Product 1

HCID 178517054HCID 178517054, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

A dry-round bottom was charged with (E)-3-((3-((E)-2-(pyridin-4-yl)vinyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-6-yl)methylene)indolin-2-one (906 mg, 1.83 mmol), and CH2Cl2 (100 mL) under an atmosphere of N2. Boron trifluoride etherate (2.3 mL, 18.3 mmol) was added dropwise and the reaction was stirred for 4 hours at which time LC-MS indicated complete conversion to the partially de-protected material (E)-3-((1-(hydroxymethyl)-3-((E)-2-(pyridin-4-yl)vinyl)-1H-indazol-6-yl)methylene)-indolin-2-one. The CH2Cl2 was removed in vacuo, and then 150 mL of a 2:1 mixture of EtOH/2M HCl was added and the reaction heated to 50° C. for 3 hours at which time LC-MS indicated complete conversion to the title compound. The reaction was cooled with an ice-bath and neutralized with NH4OH to pH˜8, the EtOH was removed and the suspension filtered washing with water. The dried solid was collected and then titurated and filtered several times with 90:10 CH2Cl2/MeOH which gave, after drying, the title compound (353 mg, 53%) as an orange solid. 1H NMR (400 MHz, d6-DMSO) δ 13.57 (s, 1H), 10.64 (s, 1H), 8.57 (d, J=5.16 Hz, 2H), 8.38 (d, J=8.13 Hz, 1H), 7.92 (s, 1H), 7.87 (d, J=16.7 Hz, 1H), 7.80 (s, 1H), 7.71 (d, J=5.16 Hz, 2H), 7.62-7.53 (m, 3H), 7.23 (t, J=8.29 Hz, 1H), 6.91-6.82 (m, 2H); MS ESI 365.1 [M+H]+, calcd for [C23H16N4O+H]+ 365.14.

Workup

  1. customThe CH2Cl2 was removed in vacuo
  2. addition150 mL of a 2:1 mixture of EtOH/2M HCl
  3. additionwas added
  4. temperatureThe reaction was cooled with an ice-bath
  5. customthe EtOH was removed
  6. filtrationthe suspension filtered
  7. washwashing with water
  8. customThe dried solid was collected
  9. filtrationfiltered several times with 90:10 CH2Cl2/MeOH which
  10. customgave
  11. customafter drying

Sources & evidence

ORD record
ord-a82224399dc141cbb3b3996f416d20ca
Source dataset
uspto-grants-2014_07
Patent number
US08765748B2

Reaction notes

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