Ethyl Acetate → HCID 86695285, compound

HRID 1057192Notes

Reaction equation

HRID 1057192 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5](/[C:8](/[CH2:38][CH3:39])=[C:9](\[C:25]2[CH:30]=[CH:29][C:28](/[CH:31]=[CH:32]/[C:33]([O:35][CH2:36][CH3:37])=[O:34])=[CH:27][CH:26]=2)/[C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[N:15]([CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][O:20]2)[N:14]=[CH:13]3)=[CH:4][CH:3]=1.[N:40]1[CH:45]=[C:44](B(O)O)[CH:43]=[N:42][CH:41]=1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:40]1[CH:45]=[C:44]([C:2]2[CH:7]=[CH:6][C:5](/[C:8](/[CH2:38][CH3:39])=[C:9](\[C:25]3[CH:26]=[CH:27][C:28](/[CH:31]=[CH:32]/[C:33]([O:35][CH2:36][CH3:37])=[O:34])=[CH:29][CH:30]=3)/[C:10]3[CH:11]=[C:12]4[C:16](=[CH:17][CH:18]=3)[N:15]([CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][O:20]3)[N:14]=[CH:13]4)=[CH:4][CH:3]=2)[CH:43]=[N:42][CH:41]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium Carbonate2×HCID 2795193(Pyrimidin-5-yl)boronic acid2×HCID 86695286HCID 86695286, compound

Product 1

HCID 86695285HCID 86695285, compoundYield 47.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 21863594Toluene ethanolSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of (E)-ethyl 3-(4-((E)-2-(4-bromophenyl)-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylate (212 mg, 0.36 mmol), pyrimidin-5-ylboronic acid (67 mg, 0.54 mmol) and potassium carbonate (100 mg, 0.72 mmol) in toluene/ethanol (4:1, 5 mL) was degassed with nitrogen. Pd(PPh3)4 (41 mg, 0.036 mmol) was added and the mixture was heated to 90° C. overnight. The reaction was not done so additional pyrimidin-5-ylboronic acid (67 mg, 0.54 mmol), potassium carbonate (100 mg, 0.72 mmol) and Pd(PPh3)4 (41 mg, 0.036 mmol) were added, and the mixture was heated to 90° C. for an additional 4 h. The mixture was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with brine (3×), dried over sodium sulfate, and purified by flash chromatography on silica gel eluting with 0 to 100% ethyl acetate/hexanes to afford 100 mg of the title compound as a yellow foam. 1H NMR (400 MHz, DMSO-d6): δ 9.16 (s, 1H), 9.15 (s, 2H), 8.13 (s, 1H), 7.76-7.67 (m, 4H), 7.48 (d, 1H), 7.42 (d, 2H), 7.35 (d, 2H), 7.26 (dd, 1H), 6.95 (d, 2H), 6.48 (d, 1H), 5.86 (dd, 1H), 4.14 (qt, 2H), 3.90 (m, 1H), 3.75 (m, 1H), 2.49-2.42 (m, 3H), 2.01 (m, 2H), 1.78 (m, 1H), 1.59 (m, 2H), 1.21 (t, 3H), 0.92 (t, 3H).

Workup

  1. customwas degassed with nitrogen
  2. additionwere added
  3. temperaturethe mixture was heated to 90° C. for an additional 4 h
  4. temperatureThe mixture was cooled to room temperature
  5. washThe organic phase was washed with brine (3×)
  6. dry with materialdried over sodium sulfate
  7. custompurified by flash chromatography on silica gel eluting with 0 to 100% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-39dbb1993d754c62859d7ddd1bb20ade
Source dataset
uspto-grants-2016_07
Patent number
US09399646B2

Reaction notes

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