Diisopropylethylamine → Benzyl (2s,3s)-2-(2-(2-(tert-butoxycarbonylamino)-5-(trifluoromethoxy)benzamido)acetamido)-3-hydroxyhex-4-ynylcarbamate

HRID 2250804Notes

Reaction equation

HRID 2250804 reaction equation
[NH2:1][CH2:2][C:3]([NH:5][C@H:6]([C@@H:19]([OH:23])[C:20]#[C:21][CH3:22])[CH2:7][NH:8][C:9](=[O:18])[O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:4].C(N(CC)C(C)C)(C)C.[C:33]([O:37][C:38]([NH:40][C:41]1[CH:49]=[CH:48][C:47]([O:50][C:51]([F:54])([F:53])[F:52])=[CH:46][C:42]=1[C:43](O)=[O:44])=[O:39])([CH3:36])([CH3:35])[CH3:34].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.CN(C=O)C>[C:33]([O:37][C:38]([NH:40][C:41]1[CH:49]=[CH:48][C:47]([O:50][C:51]([F:52])([F:53])[F:54])=[CH:46][C:42]=1[C:43]([NH:1][CH2:2][C:3]([NH:5][C@H:6]([C@@H:19]([OH:23])[C:20]#[C:21][CH3:22])[CH2:7][NH:8][C:9](=[O:18])[O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:4])=[O:44])=[O:39])([CH3:36])([CH3:34])[CH3:35]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27734412-((tert-Butoxycarbonyl)amino)-5-(trifluoromethoxy)benzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86596714benzyl (2S,3S)-2-(2-aminoacetamido)-3-hydroxyhex-4-ynylcarbamate

Product 1

HCID 90768644Benzyl (2s,3s)-2-(2-(2-(tert-butoxycarbonylamino)-5-(trifluoromethoxy)benzamido)acetamido)-3-hydroxyhex-4-ynylcarbamate

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

A solution of benzyl (2S,3S)-2-[2-(tert-butoxycarbonylamino)acetamido]-3-hydroxyhex-4-ynylcarbamate (700 mg; see WO-02/50019 for preparation) in methylene chloride (12 mL) was cooled to 0° C. and charged with trifluoroacetic acid (4 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 benzyl (2S,3S)-2-(2-aminoacetamido)-3-hydroxyhex-4-ynylcarbamate, MS found: (M+H)+=320.6. A solution of this amine in 1:1 CH2Cl2/DMF (10 mL) was charged successively with N,N-diisopropylethylamine (0.84 mL), 2-(tert-butoxycarbonylamino)-5-(trifluoromethoxy)benzoic acid (322 mg, see WO-02/50019), and HATU (544 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)-2-(2-(2-(tert-butoxycarbonylamino)-5-(trifluoromethoxy)benzamido)acetamido)-3-hydroxyhex-4-ynylcarbamate (182 mg). MS found: (M+H)+=623.3.

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-d0a5c63c163345349d46a0158c6e7e63
Source dataset
uspto-grants-2008_01
Patent number
US07317019B2

Reaction notes

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