4-Vinylpyridine → (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

HRID 1466329Notes

Reaction equation

HRID 1466329 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][C:7]([C@H:11]3[C@@:13]4([C:21]5[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=5)[NH:15][C:14]4=[O:22])[CH2:12]3)=[CH:8][CH:9]=2)[N:4]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[N:3]=1.[CH:31]([C:33]1[CH:38]=[CH:37][N:36]=[CH:35][CH:34]=1)=[CH2:32].C(N(C(C)C)CC)(C)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>CC([O-])=O.CC([O-])=O.[Pd+2].C(OCC)(=O)C.CN(C=O)C>[N:36]1[CH:37]=[CH:38][C:33](/[CH:31]=[CH:32]/[C:2]2[C:10]3[C:5](=[CH:6][C:7]([C@H:11]4[C@@:13]5([C:21]6[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=6)[NH:15][C:14]5=[O:22])[CH2:12]4)=[CH:8][CH:9]=3)[N:4]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[N:3]=2)=[CH:34][CH:35]=1

Participants

8

Reactant 4

HCID 75024-VinylpyridineHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 58486328(1R*,2S*)-2-(3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-6-yl)spiro[cyclo-propane-1,3'-indolin]-2'-one

Product 1

HCID 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'-oneYield 90%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of (1R*,2S*)-2-(3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-6-yl)spiro[cyclopropane-1,3′-indolin]-2′-one (375 mg, 0.7 mmol), 4-vinylpyridine (110 mg, 1.05 mmol), diisopropylethylamine (0.25 mL, 1.4 mmol) and DMF (2.5 mL) was added Pd(OAc)2 (8 mg, 0.035 mmol) and P(o-Tol)3 (22 mg, 0.07 mmol). The mixture was heated under microwave irradiation (130° C.) for 2 h. Ethyl acetate (150 mL) was added and the solution was washed with water (2×20 mL) and brine (20 mL), dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography (1:1 Hexane/EtOAc to 100% EtOAc) to give the title compound as a beige solid (320 mg, 90%). MS ESI 509.3 [M+H]+, calcd for [C30H32N4O2Si+H]+ 509.7.

Workup

  1. washthe solution was washed with water (2×20 mL) and brine (20 mL)
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. customThe residue was purified by silica gel chromatography (1:1 Hexane/EtOAc to 100% EtOAc)

Sources & evidence

ORD record
ord-b6e4446b9697476cae17e4c59dd49493
Source dataset
uspto-grants-2015_04
Patent number
US08999968B2

Reaction notes

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