Triethylamine → 3-(4-{4-[3-(4-Acetylpiperazin-1-yl)-2-tert-butoxycarbonylamino-3-oxo-propyl]-phenoxy}-phenyl)-propionic acid methyl ester

HRID 748990Notes

Reaction equation

HRID 748990 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][C:21]2[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][C:29]([O:31][CH3:32])=[O:30])=[CH:23][CH:22]=2)=[CH:16][CH:15]=1)[C:10](O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.[C:67]([N:70]1[CH2:75][CH2:74][NH:73][CH2:72][CH2:71]1)(=[O:69])[CH3:68]>C(Cl)Cl>[CH3:32][O:31][C:29](=[O:30])[CH2:28][CH2:27][C:24]1[CH:25]=[CH:26][C:21]([O:20][C:17]2[CH:16]=[CH:15][C:14]([CH2:13][CH:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[C:10]([N:73]3[CH2:74][CH2:75][N:70]([C:67](=[O:69])[CH3:68])[CH2:71][CH2:72]3)=[O:11])=[CH:19][CH:18]=2)=[CH:22][CH:23]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 837951-AcetylpiperazineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 597628022-Tert-butoxycarbonylamino-3-{4-[4-(2-methoxycarbonyl-ethyl)-phenoxy]-phenyl}-propionic acid

Product 1

HCID 597628063-(4-{4-[3-(4-Acetylpiperazin-1-yl)-2-tert-butoxycarbonylamino-3-oxo-propyl]-phenoxy}-phenyl)-propionic acid methyl esterYield 96%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The hydrogenated compound 4 (2.0 g, 4.6 mmol) was dissolved in CH2Cl2 (20 mL) and stirred at room temperature under an atmosphere of argon. Triethylamine (0.75 mL, 5.4 mmol) and BOP reagent (2.19 g, 4.96 mmol) were added and the reaction mixture was stirred for 15 min. 1-Acetylpiperazine (1.16 g, 9.02 mmol) was added and the resulting solution was stirred at room temperature for about 2 h. The solvent was removed under reduced pressure and the resulting oil was taken up in EtOAc (75 mL). The organic layer was extracted with 1.0 N NaOH (1×10 mL), water (2×30 mL) and brine (1×30 mL). Drying and concentration of the organic layer gave the desired amide 18 (2.4 g, ˜96%). 1H NMR (400 MHz, DMSO-d6): 7.24 (d, J=8.8 Hz, 2H), 7.19 (d, J=8.8 Hz, 2H), 6.87 (d, J=7.6 Hz, 2H), 6.83 (d, J=8.4 Hz, 2H), 4.58 (m, 1H), 3.50 (s, 3H), 3.27-3.46 (m, 8H), 3.08-3.13 (m, 1H), 2.77-2.83 (m, 3H), 2.61 (t, J=7.2 Hz, 2H), 1.99 (s, 3H), 1.32 (s, 9H).

Workup

  1. stirringthe reaction mixture was stirred for 15 min
  2. stirringthe resulting solution was stirred at room temperature for about 2 h
  3. customThe solvent was removed under reduced pressure
  4. extractionThe organic layer was extracted with 1.0 N NaOH (1×10 mL), water (2×30 mL) and brine (1×30 mL)
  5. customDrying

Sources & evidence

ORD record
ord-88e873e8f45a41d483135e3c06a16562
Source dataset
uspto-grants-2008_07
Patent number
US07399786B2

Reaction notes

Loading…