Diisopropylethylamine → Benzyl (2s,3s)-2-(2-(2-(3-ethylureido)-5-(trifluoromethyl)benzamido)acetamido)-3-hydroxyhex-4-ynylcarbamate

HRID 2250806Notes

Reaction equation

HRID 2250806 reaction equation
[NH2:1][CH2:2][C:3]([NH:5][C@H:6]([C@@H:12]([OH:16])[C:13]#[C:14][CH3:15])[CH2:7][NH:8][C:9](=[O:11])[O-:10])=[O:4].[CH:17](N(CC)C(C)C)(C)C.[CH2:26]([NH:28][C:29](=[O:44])[NH:30][C:31]1[CH:39]=[CH:38][C:37]([C:40]([F:43])([F:42])[F:41])=[CH:36][C:32]=1[C:33]([OH:35])=O)[CH3:27].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)[C:56]2[CH:57]=[CH:58][CH:59]=[CH:60][C:55]=2N=N1>C(Cl)Cl>[CH2:26]([NH:28][C:29](=[O:44])[NH:30][C:31]1[CH:39]=[CH:38][C:37]([C:40]([F:43])([F:42])[F:41])=[CH:36][C:32]=1[C:33]([NH:1][CH2:2][C:3]([NH:5][C@H:6]([C@@H:12]([OH:16])[C:13]#[C:14][CH3:15])[CH2:7][NH:8][C:9](=[O:10])[O:11][CH2:17][C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)=[O:4])=[O:35])[CH3:27]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 222687522-(3-Ethylureido)-5-(trifluoromethyl)benzoic acidHCID 86596716(2S,3S)-2-(2-aminoacetamido)-3-hydroxyhex-4-ynylcarbamate

Product 1

HCID 91439354Benzyl (2s,3s)-2-(2-(2-(3-ethylureido)-5-(trifluoromethyl)benzamido)acetamido)-3-hydroxyhex-4-ynylcarbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of benzyl (2S,3S)-2-[2-(tert-butoxycarbonylamino)acetamido]-3-hydroxyhex-4-ynylcarbamate (315 mg; see WO-02/50019 for preparation) in methylene chloride (6 mL) was cooled to 0° C. and charged with trifluoroacetic acid (2 mL). The mixture was allowed to warm to RT and stirred for 45 min before being concentrated in vacuo. The residue was dissolved in methylene chloride and the resultant solution concentrated; this was repeated twice more to afford the TFA salt of (2S,3S)-2-(2-aminoacetamido)-3-hydroxyhex-4-ynylcarbamate, MS found: (M+H)+=320.6. A solution of this amine in CH2Cl2 (8 mL) was charged successively with N,N-diisopropylethylamine (0.66 mL), 2-(3-ethylureido)-5-(trifluoromethyl)benzoic acid (208 mg, see WO-02/50019), and BOP (399 mg). The reaction was stirred for 14 h at RT before being partitioned between EtOAc and water. The organic phase was washed with sat. NH4Cl, water, and brine before being dried (Na2SO4), filtered, and concentrated in vacuo. Flash chromatography provided benzyl (2S,3S)-2-(2-(2-(3-ethylureido)-5-(trifluoromethyl)benzamido)acetamido)-3-hydroxyhex-4-ynylcarbamate (167 mg). MS found: (M+H)+=578.5.

Workup

  1. custombefore being partitioned between EtOAc and water
  2. washThe organic phase was washed with sat. NH4Cl, water, and brine
  3. dry with materialbefore being dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-74dbae9dcfde4fdb897903201786d19c
Source dataset
uspto-grants-2008_01
Patent number
US07317019B2

Reaction notes

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