Triethylamine → N1-[(1S,2R)-3-azido-1-(3,5-difluorobenzyl)-2-hydroxypropyl]5-methyl-N3,N3-dipropylisophthalamide

HRID 348806Notes

Reaction equation

HRID 348806 reaction equation
[NH2:1][C@@H:2]([CH2:9][C:10]1[CH:15]=[C:14]([F:16])[CH:13]=[C:12]([F:17])[CH:11]=1)[C@H:3]([OH:8])[CH2:4][N:5]=[N+:6]=[N-:7].[CH2:18]([N:21]([CH2:35][CH2:36][CH3:37])[C:22]([C:24]1[CH:25]=[C:26]([CH:30]=[C:31]([CH2:33]C)[CH:32]=1)[C:27](O)=[O:28])=[O:23])[CH2:19][CH3:20].C(N(CC)CC)C.C(N=C=NCCCN(C)C)C>ClCCl.C(OCC)(=O)C.CCCCCC.CO.ClCCl>[N:5]([CH2:4][C@@H:3]([OH:8])[C@@H:2]([NH:1][C:27](=[O:28])[C:26]1[CH:30]=[C:31]([CH3:33])[CH:32]=[C:24]([C:22]([N:21]([CH2:18][CH2:19][CH3:20])[CH2:35][CH2:36][CH3:37])=[O:23])[CH:25]=1)[CH2:9][C:10]1[CH:11]=[C:12]([F:17])[CH:13]=[C:14]([F:16])[CH:15]=1)=[N+:6]=[N-:7]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 225936423-[(Dipropylamino)carbonyl]-5-Ethylbenzoic AcidHCID 57428238(2R,3S)-3-amino-1-azido-4-(3,5-difluorophenyl)-2-butanol

Product 1

HCID 86585849N1-[(1S,2R)-3-azido-1-(3,5-difluorobenzyl)-2-hydroxypropyl]5-methyl-N3,N3-dipropylisophthalamide

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 21226129Dichloromethane methanolSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

To (2R, 3S)-3-amino-1-azido-4-(3,5-difluorophenyl)-2-buta (XIV, EXAMPLE 166, 0.34 g, 1.4 mmole) in dichloromethane (20 ml) is added N,N-dipropylamidoisophthalic acid (IX, 0.53 g, 2 mmole), L-butyl alcohol (0.27 g, 2 mmole) and triethylamine (0.84 ml, 6 mmole) and ethyl-1-(3-dimethylaminopropyl)carbodiimide (0.58 g, 3 mmole). The mixture is stirred at 20–25 degrees C. for 16 hours. The reaction is monitored by TLC (methanol/dichloromethane, 20/80+ethyl acetate/hexane, 50/50; Rf=0.76). When the reaction is complete as measured by TLC, the reaction mixture is partitioned between dichloromethane and water, washed with hydrochloric acid (0.5 N), bicarbonate, saline, dried over anhydrous sodium sulfate and the solvent is removed under reduced pressure with heat to produce a concentrate. The concentrate is column chouromatographed on silica gel to give the title compound; MS (MH+)=488.

Workup

  1. customthe reaction mixture is partitioned between dichloromethane and water
  2. washwashed with hydrochloric acid (0.5 N), bicarbonate, saline
  3. dry with materialdried over anhydrous sodium sulfate
  4. customthe solvent is removed under reduced pressure
  5. temperaturewith heat
  6. customto produce a concentrate

Sources & evidence

ORD record
ord-4c077116440b45a48722d09f7c70a84e
Source dataset
uspto-grants-2007_02
Patent number
US07176242B2

Reaction notes

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