Boron trifluoride etherate → (1R*,2S*)-(E)-2-(3-(2-(pyridin-4-yl)vinyl)-1H-indazol-6-yl)spiro-[cyclo-propane-1,3'-indolin]-2'-one

HRID 447514Notes

Reaction equation

HRID 447514 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]([C@H:18]4[C@@:20]5([C:28]6[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=6)[NH:22][C:21]5=[O:29])[CH2:19]4)=[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>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]([C@H:18]4[C@@:20]5([C:28]6[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=6)[NH:22][C:21]5=[O:29])[CH2:19]4)=[CH:15][CH:16]=3)[NH:11][N:10]=2)=[CH:3][CH:2]=1

Participants

4

Reactant 2

HCID 8000Boron trifluoride etherateHCID 67954877(1R*,2S*)-(E)-2-(3-(2-(pyridin-4-yl)vinyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-6-yl)spiro[cyclopropane-1,3'-indolin]-2'-one

Product 1

HCID 58486267(1R*,2S*)-(E)-2-(3-(2-(pyridin-4-yl)vinyl)-1H-indazol-6-yl)spiro-[cyclo-propane-1,3'-indolin]-2'-oneYield 93.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

A dry-round bottom was charged with (1R*,2S*)-(E)-2-(3-(2-(pyridin-4-yl)vinyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-6-yl)spiro[cyclopropane-1,3′-indolin]-2′-one (320 mg, 0.62 mmol), and CH2Cl2 (15 mL) under an atmosphere of N2. Boron trifluoride etherate (1 mL) was added dropwise and the reaction was stirred for 2 h. Methylene chloride was removed in vacuo, and then 5 mL of a 2:1 mixture of EtOH/2M HCl was added and the reaction heated to 50° C. for 2 h. The reaction was cooled with an ice-bath and neutralized with NH4OH to pH˜8, the EtOH was removed and the resulting precipitate was collected. The product was purified by silica gel chromatography (85:15 CH2Cl2/MeOH) to give the title compound as a yellow solid (220 mg, 90%). 1H NMR (400 MHz, DMSO-d6) δ 13.31 (s, 1H), 10.63 (s, 1H), 8.57-8.50 (m, 2H), 8.10 (d, J=8.1 Hz, 1H), 7.80 (d, 1H, J=16.6 Hz), 7.75-7.70 (m, 2H), 7.50-7.42 (m, 2H), 7.09-6.99 (m, 2H), 6.85 (d, 1H, J=7.6 Hz), 6.53 (t, 1H, J=7.5 Hz), 6.01 (d, 1H, J=7.8 Hz) 3.23-3.19 (m, 1H), 2.35-2.31 (m, 1H), 2.02-1.98 (m, 1H); MS ESI 379.2 [M+H]+, calcd for [C24H18N4O+H]+ 379.4.

Workup

  1. customMethylene chloride was removed in vacuo
  2. addition5 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. customthe resulting precipitate was collected
  7. customThe product was purified by silica gel chromatography (85:15 CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-bb5b347385184b8abbb614a6062f64c6
Source dataset
uspto-grants-2013_07
Patent number
US08481525B2

Reaction notes

Loading…