Diisopropylethylamine → Benzyl (2s,3s)-3-hydroxy-2-(2-(2-(3-isopropylureido)-5-(trifluoromethyl)benzamido)acetamido)hex-4-ynylcarbamate

HRID 2250805Notes

Reaction equation

HRID 2250805 reaction equation
[CH2:1]([O:8][C:9](=[O:19])[NH:10][CH2:11][C@H:12]([NH2:18])[C@@H:13]([OH:17])[C:14]#[C:15][CH3:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:20](N(CC)C(C)C)(C)C.[CH2:29]([NH:31][C:32](=[O:51])[NH:33][C:34]1[CH:46]=[CH:45][C:44]([C:47]([F:50])([F:49])[F:48])=[CH:43][C:35]=1[C:36]([NH:38][CH2:39][C:40]([OH:42])=O)=[O:37])[CH3:30].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C(Cl)Cl>[OH:17][C@@H:13]([C:14]#[C:15][CH3:16])[C@@H:12]([NH:18][C:40](=[O:42])[CH2:39][NH:38][C:36](=[O:37])[C:35]1[CH:43]=[C:44]([C:47]([F:50])([F:49])[F:48])[CH:45]=[CH:46][C:34]=1[NH:33][C:32]([NH:31][CH:29]([CH3:30])[CH3:20])=[O:51])[CH2:11][NH:10][C:9](=[O:19])[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 219911752-(2-(3-Ethylureido)-5-(trifluoromethyl)benzamido)acetic acidHCID 69196343(2S,3S)-2-amino-3-hydroxy-hex-4-ynyl-carbamic acid benzyl ester

Product 1

HCID 90910654Benzyl (2s,3s)-3-hydroxy-2-(2-(2-(3-isopropylureido)-5-(trifluoromethyl)benzamido)acetamido)hex-4-ynylcarbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (2S,3S)-[2-(tert-butoxycarbonylamino)-3-hydroxy-hex-4-ynyl]-carbamic acid benzyl ester (0.25 g, prepared as in WO PCT 0250019) in methylene chloride (9 mL) was cooled to 0° C. and charged with trifluoroacetic acid (3 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-amino-3-hydroxy-hex-4-ynyl-carbamic acid benzyl ester, MS found: (M+H)+=263.3. A solution of this amine in CH2Cl2 (12 mL) was charged successively with N,N-diisopropylethylamine (1.2 mL), 2-(2-(3-ethylureido)-5-(trifluoromethyl)benzamido)acetic acid (240 mg, see WO-02/50019), and BOP (382 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. The residue was purified by flash chromatography to afford benzyl (2S,3S)-3-hydroxy-2-(2-(2-(3-isopropylureido)-5-(trifluoromethyl)benzamido)acetamido)hex-4-ynylcarbamate (289 mg). MS found: (M+H)+=592.35.

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
  6. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-dc22558e76e34ecbb8fd269f48c2ee47
Source dataset
uspto-grants-2008_01
Patent number
US07317019B2

Reaction notes

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