4-Chloro-N-methylbenzenamine → HCID 90289970, compound

HRID 1471649Notes

Reaction equation

HRID 1471649 reaction equation
[CH3:1][C:2]([O:5][C:6]([NH:8][C@H:9]([C:18]([OH:20])=O)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([Br:17])[CH:12]=1)=[O:7])([CH3:4])[CH3:3].[Cl:21][C:22]1[CH:29]=[CH:28][C:25]([NH:26][CH3:27])=[CH:24][CH:23]=1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Br:17][C:13]1[CH:12]=[C:11]([CH2:10][C@H:9]([NH:8][C:6](=[O:7])[O:5][C:2]([CH3:1])([CH3:3])[CH3:4])[C:18]([N:26]([C:25]2[CH:28]=[CH:29][C:22]([Cl:21])=[CH:23][CH:24]=2)[CH3:27])=[O:20])[CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 702724-Chloro-N-methylbenzenamineHCID 81531DiisopropylethylamineHCID 2734476Boc-L-3-BromophenylalanineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 90289970HCID 90289970, compoundYield 82.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Boc-L-3-BromoPhe (5 g, 14.5 mmol) was dissolved in 50 mL of DMF and to it were added 4-chloro-N-methylaniline (2.1 mL, 17.4 mmol) and N,N-diisopropylethylamine (7.6 mL, 43.5 mmol). The reaction mixture was cooled to 0° C. and to it was added HATU portion wise (6.6 g, 17.4 mmol). The reaction mixture was allowed to stir at ambient temperature overnight and then was partitioned between ethyl acetate and water. The organic layer was separated and washed with 5% aqueous LiCl, saturated aqueous NaHCO3 and brine. The mixture was then dried over MgSO4, filtered and concentrated to afford crude product which was purified by silica gel chromatography eluting with ethyl acetate/hexanes to afford 5.6 g of (S)-tert-butyl 3-(3-bromophenyl)-1-((4-chlorophenyl)(methyl)amino)-1-oxopropan-2-ylcarbamate as a white solid. MS (m/z): 469.1 [M+H]+; HPLC retention time 4.39 min (5-99% acetonitrile:water with 0.05% formic acid).

Workup

  1. customwas partitioned between ethyl acetate and water
  2. customThe organic layer was separated
  3. washwashed with 5% aqueous LiCl, saturated aqueous NaHCO3 and brine
  4. dry with materialThe mixture was then dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto afford crude product which
  8. customwas purified by silica gel chromatography
  9. washeluting with ethyl acetate/hexanes

Sources & evidence

ORD record
ord-b22399e24fce447fad6a746fb5bfdaa7
Source dataset
uspto-grants-2015_04
Patent number
US09012441B2

Reaction notes

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