Butyl iodide → (E)-ethyl 3-(4-((E)-2-(3-butoxyphenyl)-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylate

HRID 1254461Notes

Reaction equation

HRID 1254461 reaction equation
C(=O)([O-])[O-].[K+].[K+].[OH:7][C:8]1[CH:9]=[C:10](/[C:14](/[CH2:44][CH3:45])=[C:15](\[C:31]2[CH:36]=[CH:35][C:34](/[CH:37]=[CH:38]/[C:39]([O:41][CH2:42][CH3:43])=[O:40])=[CH:33][CH:32]=2)/[C:16]2[CH:17]=[C:18]3[C:22](=[CH:23][CH:24]=2)[N:21]([CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][O:26]2)[N:20]=[CH:19]3)[CH:11]=[CH:12][CH:13]=1.I[CH2:47][CH2:48][CH2:49][CH3:50]>CC#N.ClCCl>[CH2:47]([O:7][C:8]1[CH:9]=[C:10](/[C:14](/[CH2:44][CH3:45])=[C:15](\[C:31]2[CH:32]=[CH:33][C:34](/[CH:37]=[CH:38]/[C:39]([O:41][CH2:42][CH3:43])=[O:40])=[CH:35][CH:36]=2)/[C:16]2[CH:17]=[C:18]3[C:22](=[CH:23][CH:24]=2)[N:21]([CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][O:26]2)[N:20]=[CH:19]3)[CH:11]=[CH:12][CH:13]=1)[CH2:48][CH2:49][CH3:50]

Participants

6

Reactant 3

HCID 10962Butyl iodide2×HCID 11430Potassium CarbonateHCID 66794676(E)-ethyl 3-(4-((E)-2-(3-hydroxyphenyl)-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylate

Product 1

HCID 66794921(E)-ethyl 3-(4-((E)-2-(3-butoxyphenyl)-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylateYield 88.2%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

Potassium carbonate (53 mg, 0.38 mmol) was added to (E)-ethyl 3-(4-((E)-2-(3-hydroxyphenyl)-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylate (101 mg, 0.19 mmol) in CH3CN (1 mL). After stirring for 15 min, iodobutane (24 μL, 0.21 mmol) was added. The reaction was stirred at rt for 15 h. Additional iodobutane (24 μL, 0.21 mmol) was added, and the reaction was stirred at 60° C. for 10 h and then at rt for 48 h. The reaction was diluted with dichloromethane and filtered through celite. The filtrate was concentrated and purified by silica gel chromatography (0˜20% EtOAc in hexanes) to give 97 mg of (E)-ethyl 3-(4-((E)-2-(3-butoxyphenyl)-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylate as a white foam. 1H NMR (400 MHz, DMSO-d6): δ 8.12 (s, 1H), 7.73 (d, 1H), 7.64 (s, 1H), 7.49 (d, 1H), 7.41 (d, 2H), 7.24 (dd, 1H), 7.12 (t, 1H), 6.91 (d, 2H), 6.76 (d, 1H), 6.67-6.72 (m, 2H), 6.48 (d, 1H), 5.86 (d, 1H), 4.15 (q, 2H), 3.86-3.94 (m, 1H), 3.72-3.80 (m, 3H), 2.38-2.46 (m, 3H), 1.96-2.10 (m, 2H), 1.70-1.82 (m, 1H), 1.52-1.63 (m, 4H), 1.31-1.37 (m, 2H), 1.22 (t, 3H), 0.85-0.92 (m, 6H); LCMS: 495 [(M-THP+H)+H]+.

Workup

  1. stirringThe reaction was stirred at rt for 15 h
  2. stirringthe reaction was stirred at 60° C. for 10 h
  3. waitat rt for 48 h
  4. filtrationfiltered through celite
  5. concentrationThe filtrate was concentrated
  6. custompurified by silica gel chromatography (0˜20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-780201e19e9d4e59b233d6885b01f3ff
Source dataset
uspto-grants-2013_06
Patent number
US08455534B2

Reaction notes

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