Tetrabutylammonium Fluoride → (1R*,2S*)-5'-Methoxy-2-(3-(6-morpholinopyridin-3-yl)-1H-indazol-6-yl)spiro[cyclopropane-1,3'-indolin]-2'-one

HRID 2383646Notes

Reaction equation

HRID 2383646 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[C@:6]12[CH2:14][C@H:13]1[C:15]1[CH:23]=[C:22]2[C:18]([C:19]([C:32]3[CH:33]=[N:34][C:35]([N:38]4[CH2:43][CH2:42][O:41][CH2:40][CH2:39]4)=[CH:36][CH:37]=3)=[N:20][N:21]2COCC[Si](C)(C)C)=[CH:17][CH:16]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.CCOC(C)=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[C@:6]12[CH2:14][C@H:13]1[C:15]1[CH:23]=[C:22]2[C:18]([C:19]([C:32]3[CH:33]=[N:34][C:35]([N:38]4[CH2:43][CH2:42][O:41][CH2:40][CH2:39]4)=[CH:36][CH:37]=3)=[N:20][NH:21]2)=[CH:17][CH:16]=1

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 67955021(1R*,2S*)-5'-Methoxy-2-(3-(6-morpholinopyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)-methyl)-1H-indazol-6-yl)spiro[cyclopropane-1,3'-indolin]-2'-one

Product 1

HCID 58486131(1R*,2S*)-5'-Methoxy-2-(3-(6-morpholinopyridin-3-yl)-1H-indazol-6-yl)spiro[cyclopropane-1,3'-indolin]-2'-oneYield 53.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (1R*,2S*)-5′-methoxy-2-(3-(6-morpholinopyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-6-yl)spiro[cyclopropane-1,3′-indolin]-2′-one (10 mg, 0.02 mmol) in THF (2.0 mL) was treated with TBAF (0.10 mL, 1M in THF) and refluxed for 3 h. The reaction was diluted with EtOAc and the organic layer was washed with brine (4×) and then dried over MgSO4. The solvent was removed and the crude product was purified by silica gel chromatography using EtOAc as eluent followed by trituration (EtOAc: Hexanes, 1:1) to give the title compound as a yellow powder (5 mg, 13%). 1H NMR (400 MHz, CD3OD) δ 8.70 (d, J=2.4 Hz, 1H), 8.14 (dd, J=8.8, 2.4 Hz, 1H), 7.89 (d, J=8.5 Hz, 1H), 7.50 (s, 1H), 7.04 (d, J=7.5 Hz, 1H), 6.98 (d, J=8.9 Hz, 1H), 6.83 (d, J=8.5 Hz, 1H), 6.62 (dd, J=8.5, 2.6 Hz, 1H), 5.61 (d, J=2.5, 1H), 4.63 (s, 1H), 3.84 (t, J=4.8 Hz, 4H), 3.58 (t, J=5.0 Hz, 4H), 3.40-3.35 (m, 1H), 3.29 (s, 3H), 2.28-2.25 (m, 1H), 2.21-2.18 (m, 1H); MS ESI 468.3 [M+H]+, calcd for [C27H25N5O3+H]+ 468.20.

Workup

  1. temperaturerefluxed for 3 h
  2. washthe organic layer was washed with brine (4×)
  3. dry with materialdried over MgSO4
  4. customThe solvent was removed
  5. customthe crude product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-3e219bdfc4904b70a19b3d1bbffcaf3b
Source dataset
uspto-grants-2012_09
Patent number
US08263596B2

Reaction notes

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