1-Octyne → Ethyl 3-(5-(oct-1-ynyl)indoline-1-carboxamido)propanoate

HRID 717639Notes

Reaction equation

HRID 717639 reaction equation
I[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]([NH:13][CH2:14][CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])=[O:12])[CH2:6][CH2:5]2.[CH:21]#[C:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28]>[Cu]I>[C:21]([C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]([NH:13][CH2:14][CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])=[O:12])[CH2:6][CH2:5]2)#[C:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28]

Participants

4

Reactant 2

HCID 123701-OctyneHCID 66614968Ethyl 3-(5-iodoindoline-1-carboxamido)propanoate

Product 1

HCID 66615094Ethyl 3-(5-(oct-1-ynyl)indoline-1-carboxamido)propanoateYield 65.8%

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Procedure

A mixture of the product of Step B (0.16 g; 0.41 mmol), 1-octyne (0.073 ml; 0.49 mmol), Cl2Pd(PPh3)2 (0.02 g; 0.028 mmol) and CuI (0.005 g; 0.026 mmol) was degassed under reduced pressure and saturated with dry N2. After addition of DIPEA (0.5 ml), the resulting mixture was stirred for 2 h at room temperature under N2. The solvents were removed in vacuo and the residue was diluted to 15 ml with EtOAc and washed with 5% citric acid, 5% NaHCO3, H2O, brine and dried over anhydrous MgSO4 and filtered. The filtrate was evaporated to dryness under reduced pressure and the residue was purified by FCC (SiO2; CH2Cl2) to give the title compound (0.1 g; 65%) as a brownish solid. 1H-NMR (CDCl3) 7.75 (d, 1H, J=8.4 Hz); 7.16 (d, 1H, J=8.4 Hz); 7.1 (s, 1H); 5.34 (1, 1H, J=5.8 Hz); 4.11 (q, 2H, J=7.1 Hz); 3.82 (t, 2H, J=8.8 Hz); 3.52 (m, 2H); 3.06 (t, 2H, J=8.8 Hz); 2.56 (t, 2H, J=5.8 Hz); 2.33 (t, 2H, J=7.1 Hz); 1.53 (m, 2H); 1.52 (m, 2H); 1.26 (m, 6H); 1.23 (t, 2H, J=7.1 Hz); 0.86 (1, 3H, J=6.9 Hz).

Workup

  1. customwas degassed under reduced pressure and saturated with dry N2
  2. additionAfter addition of DIPEA (0.5 ml)
  3. customThe solvents were removed in vacuo
  4. additionthe residue was diluted to 15 ml with EtOAc
  5. washwashed with 5% citric acid, 5% NaHCO3, H2O, brine
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. customThe filtrate was evaporated to dryness under reduced pressure
  9. customthe residue was purified by FCC (SiO2; CH2Cl2)

Sources & evidence

ORD record
ord-4c0a7f367ecd4564b0cebb63189a1a31
Source dataset
uspto-grants-2015_11
Patent number
US09193716B2

Reaction notes

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