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 2069587Notes

Reaction equation

HRID 2069587 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)acrylate

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)phenypacrylate 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)
  7. customto 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)phenypacrylate as a white foam

Sources & evidence

ORD record
ord-5d8704ebd37c4b8ea734e8f0d8972fcb
Source dataset
uspto-grants-2012_10
Patent number
US08299112B2

Reaction notes

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