Urea → HCID 91423880, compound

HRID 2417450Notes

Reaction equation

HRID 2417450 reaction equation
[NH2:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][C@H:7]([N:10]([CH2:18][C@@H:19]([OH:28])[CH2:20][O:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH2:8][OH:9])=[CH:4][CH:3]=1.[CH3:31]/[C:32](/O[Si](C)(C)C)=N\[Si](C)(C)C.[N-]=[C:44]=[O:45].N[C:47](N)=O.[CH:50]([N:53]([CH2:57][CH3:58])[CH:54]([CH3:56])[CH3:55])(C)C.FC(F)(F)C(O)=O>CN1CCCC1=O.O>[OH:9][CH2:8][C@@H:7]([N:10]([CH2:18][C@H:19]([OH:28])[CH2:20][O:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH2:6][C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:44]([C:58]2[C:56]3[C:54](=[CH:55][CH:47]=[CH:32][CH:31]=3)[N:53]([CH3:50])[CH:57]=2)=[O:45])=[CH:30][CH:29]=1

Participants

9

Reactant 6

HCID 1176UreaHCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 105034IsocyanateHCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 69818731HCID 69818731, compound

Product 1

HCID 91423880HCID 91423880, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent4×

Procedure

To a solution of tert-butyl N-[(1S)-1-(4-aminobenzyl)-2-hydroxyethyl]-N-[(2R)-2-hydroxy-3-phenoxypropyl]carbamate (0.02 mmol) in N-methyl-2-pyrrolidinone (NMP) (40 μl) was added 2.0 M solution of N,O-bis(trimethylsilyl)acetamide (BSA) in NMP (10 pl, 0.02 mmol) at room temperature. After stirring for 30 minutes, 1.0 M solution of an isocyanate derivative (O═C=N—B) corresponding to an objective urea derivative in NMP (24 pl, 0.024 mmol) and 0.1 M solution of N,N-diisopropylethylamine (DIEA) in NMP (20 μl, 0.002 mmol) were added to the solution. After further stirring at 50° C. for 30 minutes, the reaction mixture was treated with 95% trifluoroacetic acid (TFA) in water (500 μl) at 50° C. for 30 minutes. The mixture was concentrated under reduced pressure and the residue was purified by HPLC (reverse phase C18, 0-80% 0.1% TFA in acetonitrile/0.1% TFA in water). The fractions containing the desired compound were combined, concentrated and dried under reduced pressure to give the objective urea derivative (7).

Workup

  1. stirringAfter further stirring at 50° C. for 30 minutes
  2. concentrationThe mixture was concentrated under reduced pressure
  3. customthe residue was purified by HPLC (reverse phase C18, 0-80% 0.1% TFA in acetonitrile/0.1% TFA in water)
  4. additionThe fractions containing the desired compound
  5. concentrationconcentrated
  6. customdried under reduced pressure

Sources & evidence

ORD record
ord-0c792d64032a4769af5d4d0154ee0cc6
Source dataset
uspto-grants-2004_11
Patent number
US06826033B2

Reaction notes

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