Dimethylamine → (Dimethylcarbamoyl-{4-[4-(2-dimethylcarbamoylethyl)-phenoxy]-phenyl}-methyl)-carbamic acid tert-butyl ester

HRID 749011Notes

Reaction equation

HRID 749011 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([C:28](=[O:32])[N:29]([CH3:31])[CH3:30])[C:10]1[CH:27]=[CH:26][C:13]([O:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][C:23](O)=[O:24])=[CH:17][CH:16]=2)=[CH:12][CH:11]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:33]([N:35](CC)[CH2:36]C)C.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.CNC>C(Cl)Cl>[C:1]([O:5][C:6](=[O:7])[NH:8][CH:9]([C:28](=[O:32])[N:29]([CH3:31])[CH3:30])[C:10]1[CH:27]=[CH:26][C:13]([O:14][C:15]2[CH:16]=[CH:17][C:18]([CH2:21][CH2:22][C:23](=[O:24])[N:35]([CH3:36])[CH3:33])=[CH:19][CH:20]=2)=[CH:12][CH:11]=1)([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 4

HCID 674DimethylamineHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 597511203-{4-[4-(Tert-butoxycarbonylaminodimethylcarbamoylmethyl)-phenoxy]-phenyl}-propionic acid

Product 1

HCID 57439944(Dimethylcarbamoyl-{4-[4-(2-dimethylcarbamoylethyl)-phenoxy]-phenyl}-methyl)-carbamic acid tert-butyl esterYield 94.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Acid compound 33 (0.7 g, 1.58 mmol) was dissolved in DCM (20 mL) and stirred at room temp under an atmosphere of argon. Triethylamine (0.26 mL, 1.9 mmol) and BOP reagent (0.77 g, 1.74 mmol) were added and the reaction mixture was stirred for 15 min. Dimethylamine (2.0 M solution in THF, 4.0 mL, 7.9 mmol) was added and the resulting solution was stirred at room temp 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 40 (0.7 g, 94.5%). 1H NMR (400 MHz, DMSO-d6): 7.33 (d, J=8.4 Hz, 2H), 7.26 (d, J=8.4 Hz, 2H), 7.11 (d, J=8.0 Hz, 1H), 6.93 (overlapped d, J=8.4 Hz, 2H), 6.92 (overlapped d, J=8.4 Hz, 2H), 5.50 (d, J=7.6 Hz, 2H), 2.93 (s, 3H), 2.90 (s, 3H), 2.84 (s, 3H), 2.82 (s, 3H), 2.79 (t, J=8.0 Hz, 2H), 2.59 (t, J=8.0 Hz, 2H), 1.37 (s, 9H).

Workup

  1. stirringthe reaction mixture was stirred for 15 min
  2. stirringthe resulting solution was stirred at room temp 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-5ae1ca7fc82a4583a1b78792502ae0ea
Source dataset
uspto-grants-2008_07
Patent number
US07399786B2

Reaction notes

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