Urea → HCID 91453837, compound

HRID 2417451Notes

Reaction equation

HRID 2417451 reaction equation
[NH2:1][C:2]1[CH:29]=[CH:28][C:5]([CH2:6][C@H:7]([N:10]([CH2:18][C@@H:19](C2C=CC=C(Cl)C=2)[OH:20])[C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH2:8][OH:9])=[CH:4][CH:3]=1.[CH3:30]/[C:31](/[O:37][Si](C)(C)C)=N\[Si](C)(C)C.[N-]=[C:43]=[O:44].N[C:46](N)=O.[CH:49](N(CC)C(C)C)([CH3:51])[CH3:50].F[C:59](F)(F)[C:60](O)=O.C[N:66]1C[CH2:69][CH2:68][C:67]1=O>O>[OH:20][C@H:19]([CH2:46][O:44][C:43]1[CH:60]=[CH:59][CH:51]=[CH:49][CH:50]=1)[CH2:18][N:10]([C@@H:7]([CH2:6][C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:31]([C:30]2[NH:66][CH:67]=[CH:68][CH:69]=2)=[O:37])=[CH:29][CH:28]=1)[CH2:8][OH:9])[C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:14])[CH3:15]

Participants

9

Reactant 7

HCID 1176UreaHCID 6422Trifluoroacetic acidHCID 13387N-methyl-2-pyrrolidone4×HCID 81531DiisopropylethylamineHCID 105034IsocyanateHCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 69817835HCID 69817835, compound

Product 1

HCID 91453837HCID 91453837, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of tert-butyl N-[(1s)-1-(4-aminobenzyl)-2-hydroxyethyl]-N-[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]-carbamate (0.02 mmol) in NMP (40 ul) was added 2.0 M solution of N,O-bis(trimethylsilyl)acetamide (BSA) in N-methyl-2-pyrrolidinone (NMP) (10 μl, 0.02 mmol) and the mixture was shaken for 30 minutes at room temperature. To the solution, 1.0 M solution of an isocyanate derivative (O═C═N—B) corresponding to an objective urea derivative in NMP (24 μl, 0.024 mmol) and 0.1 M solution of N,N-diisopropylethylamine (DIEA) in NMP (20 μl, 0.002 mmol) were added and the mixture was shaken for 30 minutes at 50° C. After cooling to room temperature, 0.5 ml of 95% trifluoroacetic acid (TFA) in water was added to the solution and shaken for 15 hours. The mixture was concentrated under reduced pressure and 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 (9).

Workup

  1. stirringthe mixture was shaken for 30 minutes at 50° C
  2. temperatureAfter cooling to room temperature
  3. stirringshaken for 15 hours
  4. concentrationThe mixture was concentrated under reduced pressure
  5. custompurified by HPLC (reverse phase C18, 0-80% 0.1% TFA in acetonitrile/0.1% TFA in water)
  6. additionThe fractions containing the desired compound
  7. concentrationconcentrated
  8. customdried under reduced pressure

Sources & evidence

ORD record
ord-3189767442044f8ebc05e0ebaf4c95e6
Source dataset
uspto-grants-2004_11
Patent number
US06826033B2

Reaction notes

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