Dimethylamine → HCID 76573112, compound

HRID 2111871Notes

Reaction equation

HRID 2111871 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][CH:28]3[S:32][C:31](=[O:33])[NH:30][C:29]3=[O:34])=[CH:23][CH:22]=2)=[CH:16][CH:15]=1)[C:10](O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)[N:53]([CH3:55])[CH3:54])C2C=CC=CC=2N=N1.CNC>C(Cl)Cl.C(N(CC)CC)C>[C:1]([O:5][C:6](=[O:7])[NH:8][CH:9]([C:10](=[O:11])[N:53]([CH3:55])[CH3:54])[CH2:13][C:14]1[CH:15]=[CH:16][C:17]([O:20][C:21]2[CH:26]=[CH:25][C:24]([CH2:27][CH:28]3[S:32][C:31](=[O:33])[NH:30][C:29]3=[O:34])=[CH:23][CH:22]=2)=[CH:18][CH:19]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 674DimethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 10345313HCID 10345313, compound

Product 1

HCID 76573112HCID 76573112, compoundYield 13.8%

Reagents, catalysts & solvents 2

HCID 8471TriethylamineCatalystHCID 6344DichloromethaneSolvent

Procedure

The compound, 2-tert-butoxycarbonylamino-3-{4-[4-(2,4-dioxothiazolidin-5-ylmethyl)-phenoxy]-phenyl}-propionic acid (4.2 g, 8.63 mmol) was dissolved in CH2Cl2 (30 mL) and stirred at room temperature under an atmosphere of argon. Triethylamine (1.44 mL, 0.014 mmol) and benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP reagent, 4.19 g, 9.5 mmol) were added and the reaction mixture was stirred for 15 min. Dimethylamine (2.0 M solution in THF, 5.6 mL, 11.2 mmol) was added and the resulting solution was stirred at room temperature for about 1 h. The solvent was removed under reduced pressure and the resulting oil was taken up in EtOAc (100 mL). The organic layer was extracted with 0.5 N NaOH (1×50 mL), water (1×100 mL) and brine (1×100 mL). Silica gel chromatography of the crude product with CHCl3-MeOH (19:1) yielded pure amide, (1-dimethylcarbamoyl-2-{4-[4-(2,4-dioxothiazolidin-5-ylmethyl)-phenoxy]-phenyl}-ethyl)-carbamic acid tert-butyl ester (0.61 g, 13.8%). 1H NMR (400 MHz, CDCl3): 7.17 (overlapped d, J=8.4 Hz, 2H), 7.16 (overlapped d, J=8.4 Hz, 2H), 6.92 (overlapped d, J=8.4 Hz, 2H), 6.90 (overlapped d, J=8.4 Hz, 2H), 5.51 (d, J=8.4 Hz, 1H), 4.81 (m, 1H), 3.02-3.13 (m, 2H), 2.83-2.95 (m, 5H), 2.76 (s, 3H), 1.46 (s, 9H).

Workup

  1. stirringthe reaction mixture was stirred for 15 min
  2. stirringthe resulting solution was stirred at room temperature for about 1 h
  3. customThe solvent was removed under reduced pressure
  4. extractionThe organic layer was extracted with 0.5 N NaOH (1×50 mL), water (1×100 mL) and brine (1×100 mL)

Sources & evidence

ORD record
ord-db1c5a2b2a5a43dda8e4d6fd1b87fdba
Source dataset
uspto-grants-2009_04
Patent number
US07521465B2

Reaction notes

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