Dimethylamine → HCID 59762818, compound

HRID 748977Notes

Reaction equation

HRID 748977 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]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:33]([N:35](CC)[CH2:36]C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CNC>C(Cl)Cl>[CH3:32][O:31][C:29](=[O:30])[CH2:28][CH2:27][C:24]1[CH:23]=[CH:22][C:21]([O:20][C:17]2[CH:18]=[CH:19][C:14]([CH2:13][CH:9]([NH:8][C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:7])[C:10](=[O:12])[N:35]([CH3:36])[CH3:33])=[CH:15][CH:16]=2)=[CH:26][CH:25]=1

Participants

6

Reactant 4

HCID 674DimethylamineHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 597628022-Tert-butoxycarbonylamino-3-{4-[4-(2-methoxycarbonyl-ethyl)-phenoxy]-phenyl}-propionic acid

Product 1

HCID 59762818HCID 59762818, compoundYield 99.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The hydrogenated compound 4 (8.0 g, 18.0 mmol) was dissolved in CH2Cl2 and stirred at room temperature under an atmosphere of argon. Triethylamine (3.02 mL, 21.6 mmol) and benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP reagent, 8.78 g, 20.0 mmol) were added and the reaction mixture was stirred for 15 min. Dimethylamine (2.0 M solution in THF, 45.2 mL, 90.0 mmol) was added and the resulting solution was stirred at room temperature for about 2-3 h. The solvent was removed under reduced pressure and the resulting oil was taken up in EtOAc (200 mL). The organic layer was extracted with 0.5 N NaOH (1×30 mL), water (2×100 mL) and brine (1×100 mL). Drying and concentration of the organic layer gave the desired amide 5 (8.4 g, ˜98%). 1H NMR (400 MHz, DMSO-d6): 7.24 (d, J=8.4 Hz, 2H), 7.20 (d, J=8.4 Hz, 2H), 7.07 (d, J=8.4 Hz, 1H), 6.89 (d, J=8.8 Hz, 2H), 6.86 (d, J=8.8 Hz, 2H), 4.23 (m, 1H), 3.58 (s, 3H), 2.91 (s, 3H), 2.70-2.86 (m, 7H), 2.62 (t, J=7.6 Hz, 2H), 1.31 (s, 9H).

Workup

  1. stirringthe reaction mixture was stirred for 15 min
  2. stirringthe resulting solution was stirred at room temperature for about 2-3 h
  3. customThe solvent was removed under reduced pressure
  4. extractionThe organic layer was extracted with 0.5 N NaOH (1×30 mL), water (2×100 mL) and brine (1×100 mL)
  5. customDrying

Sources & evidence

ORD record
ord-17b227fe16c84f63951050146f417493
Source dataset
uspto-grants-2008_07
Patent number
US07399786B2

Reaction notes

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