methyl (2E)-3-(4-formylphenyl)prop-2-enoate → HCID 117719352, compound

HRID 1749023Notes

Reaction equation

HRID 1749023 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][C@H:11]([NH:13][CH2:14][C:15]([F:18])([CH3:17])[CH3:16])[CH3:12])=[CH:2]1.[CH:19]([C:21]1[CH:26]=[CH:25][C:24](/[CH:27]=[CH:28]/[C:29]([O:31][CH3:32])=[O:30])=[CH:23][CH:22]=1)=O>C1(C)C=CC=CC=1>[F:18][C:15]([CH3:17])([CH3:16])[CH2:14][N:13]1[C@H:11]([CH3:12])[CH2:10][C:3]2[C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[NH:1][C:2]=2[C@H:19]1[C:21]1[CH:22]=[CH:23][C:24](/[CH:27]=[CH:28]/[C:29]([O:31][CH3:32])=[O:30])=[CH:25][CH:26]=1

Participants

4

Reactant 2

HCID 11008713methyl (2E)-3-(4-formylphenyl)prop-2-enoateHCID 117719359(R)-N-(1-(1H-indol-3-yl)propan-2-yl)-2-fluoro-2-methylpropan-1-amine

Product 1

HCID 117719352HCID 117719352, compoundYield 41.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

(R)—N-(1-(1H-indol-3-yl)propan-2-yl)-2-fluoro-2-methylpropan-1-amine (obtained as described in Example 1, preparation of starting materials) (450 mg, 1.81 mmol) and (E)-methyl 3-(4-formylphenyl)acrylate (345 mg, 1.81 mmol) were dissolved in toluene (15 ml) acetic acid (5 ml) and molecular sieves were added. The reaction was stirred at 110° C. for 16 hours under nitrogen then cooled to room temperature. The crude product was purified by ion exchange chromatography, using an SCX-2 column. The desired product was eluted from the column using 7M NH3/methanol and pure fractions were evaporated to dryness to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in heptane. Pure fractions were evaporated to dryness to afford (E)-methyl 3-(4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylate (317 mg, 41.6%) as a yellow solid. 1H NMR (400 MHz, CDCl3, 30° C.) δ 1.09 (3H, d), 1.30 (3H, d), 1.47 (3H, d), 2.48-2.78 (4H, m), 3.30 (1H, m), 3.79 (3H, s) 5.09 (1H, s) 6.40 (1H, d), 7.12 (1H, td), 7.17 (1H, td), 7.29 (1H, d), 7.34 (2H, d), 7.43 (2H, d), 7.54 (1H, d), 7.66 (2H, nm). m/z: ES+ [M+H]+ 421.

Workup

  1. additionmolecular sieves were added
  2. temperaturethen cooled to room temperature
  3. customThe crude product was purified by ion exchange chromatography
  4. washThe desired product was eluted from the column
  5. customwere evaporated to dryness
  6. customto afford crude product
  7. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in heptane
  8. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-f77d62a0d1f446c09c8a152221375ce9
Source dataset
uspto-grants-2015_10
Patent number
US09155727B2

Reaction notes

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