(2R)-1-(1H-INDOL-3-YL)PROPAN-2-AMINE → HCID 117719364, compound

HRID 1749027Notes

Reaction equation

HRID 1749027 reaction equation
[CH:1]([C:3]1[CH:8]=[CH:7][C:6](/[CH:9]=[CH:10]/[C:11]([O:13][CH3:14])=[O:12])=[CH:5][CH:4]=1)=O.[NH:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:17]([CH2:24][C@H:25]([NH2:27])[CH3:26])=[CH:16]1>C(O)(=O)C>[CH3:26][C@H:25]1[NH:27][C@@H:1]([C:3]2[CH:8]=[CH:7][C:6](/[CH:9]=[CH:10]/[C:11]([O:13][CH3:14])=[O:12])=[CH:5][CH:4]=2)[C:16]2[NH:15][C:23]3[C:18]([C:17]=2[CH2:24]1)=[CH:19][CH:20]=[CH:21][CH:22]=3

Participants

4

Reactant 2

HCID 448779(2R)-1-(1H-INDOL-3-YL)PROPAN-2-AMINEHCID 11008713methyl (2E)-3-(4-formylphenyl)prop-2-enoate

Product 1

HCID 117719364HCID 117719364, compoundYield 74.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
80 °C

Procedure

(E)-Methyl 3-(4-formylphenyl)acrylate (obtained as described in Example 2, preparation of starting materials) (18.56 g, 97.57 mmol) was added to a stirred solution of (R)-1-(1H-indol-3-yl)propan-2-amine (17 g, 97.57 mmol) in acetic acid (250 mil) at 23° under nitrogen. The resulting solution was stirred at 80° C. for 2 hours. The reaction mixture was evaporated to dryness and redissolved in DCM (500 ml), and washed sequentially with saturated NaHCO3 (300 ml×2), 2M NaOH (aq) (300 ml), water (300 ml), and saturated brine (300 ml). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 1 to 7% methanol in DCM. Pure fractions were evaporated to dryness to afford (E)-methyl 3-(4-((1S,3R)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylate (25.1 g, 74.3%) as a beige foam. The product was mostly cis isomer, containing about 12% trans isomer which was inseparable. 1H NMR (400 MHz, DMSO, 30° C.) δ 1.25 (3H, d), 2.37-2.48 (1H, m), 2.74 (1H, d), 3.12 (1H, s), 3.73 (3H, s), 5.18 (1H, s), 6.64 (1H, d), 6.97 (2H, dd), 7.19 (1H, d), 7.36-7.46 (3H, m), 7.64-7.75 (3H, m), 10.19 (1H, s), no NH observed. m/z: ES+ [M+H]+ 347.

Workup

  1. customThe reaction mixture was evaporated to dryness
  2. dissolutionredissolved in DCM (500 ml)
  3. washwashed sequentially with saturated NaHCO3 (300 ml×2), 2M NaOH (aq) (300 ml), water (300 ml), and saturated brine (300 ml)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customto afford crude product
  8. customThe crude product was purified by flash silica chromatography, elution gradient 1 to 7% methanol in DCM
  9. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-aa94095337f74c4cac76467136f2980c
Source dataset
uspto-grants-2015_10
Patent number
US09155727B2

Reaction notes

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