Dichloromethane → HCID 178487099, compound

HRID 1466258Notes

Reaction equation

HRID 1466258 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[N:13]=[CH:12][C:11](/[CH:14]=[CH:15]/[C:16]3[C:24]4[C:19](=[CH:20][C:21]([CH:25]=[C:26]5[C:34]6[C:29](=[CH:30][CH:31]=CC=6)[NH:28][C:27]5=[O:35])=[CH:22][CH:23]=4)[N:18](COCC[Si](C)(C)C)[N:17]=3)=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.B(F)(F)F.C[CH2:49][O:50][CH2:51][CH3:52].C(Cl)[Cl:54]>>[ClH:54].[ClH:54].[CH3:49][O:50][C:51]1[CH:52]=[C:34]2[C:29](=[CH:30][CH:31]=1)[NH:28][C:27](=[O:35])[C:26]2=[CH:25][C:21]1[CH:20]=[C:19]2[C:24]([C:16](/[CH:15]=[CH:14]/[C:11]3[CH:12]=[N:13][C:8]([N:5]4[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]4)=[CH:9][CH:10]=3)=[N:17][NH:18]2)=[CH:23][CH:22]=1

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 8000Boron trifluoride etherateHCID 131732691HCID 131732691, compound

Product 1

HCID 178487099HCID 178487099, compound

Procedure

To a DCM (50 mL) solution of 5-methoxy-3-(E & Z)-((3-((E)-2-(6-(4-methylpiperazin-1-yl)-pyridin-3-yl)vinyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-6-yl)methyl-ene)indolin-2-one (0.85 g, 1.36 mmol) was added BF3.OEt2 (1.7 mL, 13.6 mmol) at 0° C. The cooling bath was removed and the reaction mixture was stirred for 4 h. After removal of the solvent under reduced pressure, the residue was heated in EtOH (40 mL) and 2 M aq HCl (20 mL) at 60° C. overnight. The reaction was then stored at 5° C. overnight. A red precipitate was collected and washed separately with EtOAc, MeCN and Et2O to provide the title compound as as a 3.3:1 (E:Z) mixture of isomers: an orange-red powder (0.32 g, 42%). 1H NMR (400 MHz, CD3OD) 8 ppm 8.87 (s, 0.3 H), 8.53-8.61 (m, 1.0 H), 8.28-8.32 (m, 1H), 8.26 (d, J=8.53 Hz, 0.7 H), 8.13 (d, J=8.28 Hz, 0.3 H), 8.00 (t, J=7.99 Hz, 0.3 H), 7.95-8.02 (m, 1.5 H), 7.83-7.90 (m, 3.3 H), 7.30 (d, J=2.3 Hz, 0.3 H), 7.24 (s, 0.7 H), 6.84 (s, 1.4 H), 6.76-6.84 (m, 0.4 H), 4.39-4.59 (br.s, 2 H), 3.64-3.85 (br.s., 4 H), 3.63 (s, 3 H), 3.32-3.60 (br.s., 2 H), 3.03 (s, 3 H); MS ESI [M+H]+ 493.3, calcd for [C29H28N6O2+H]+ 493.6.

Workup

  1. customThe cooling bath was removed
  2. customAfter removal of the solvent under reduced pressure
  3. temperaturethe residue was heated in EtOH (40 mL)
  4. customat 60° C.
  5. customovernight
  6. waitThe reaction was then stored at 5° C. overnight
  7. customA red precipitate was collected
  8. washwashed separately with EtOAc, MeCN and Et2O

Sources & evidence

ORD record
ord-3902523752694cbfbd56d9cd7adcfab8
Source dataset
uspto-grants-2015_04
Patent number
US08999968B2

Reaction notes

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