Diisopropylethylamine → benzyl (2S,3S)-2-(3-(3-(tert-butoxycarbonyl)amino-5-(trifluoromethyl)phenylamino)-3-oxopropanamido)-3-hydroxyhex-4-ynylcarbamate

HRID 2250810Notes

Reaction equation

HRID 2250810 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.C(N(CC)C(C)C)(C)C.[C:29]([O:33][C:34]([NH:36][C:37]1[CH:38]=[C:39]([NH:47][C:48](=[O:53])[CH2:49][C:50](O)=[O:51])[CH:40]=[C:41]([C:43]([F:46])([F:45])[F:44])[CH:42]=1)=[O:35])([CH3:32])([CH3:31])[CH3:30].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:29]([O:33][C:34]([NH:36][C:37]1[CH:38]=[C:39]([NH:47][C:48](=[O:53])[CH2:49][C:50]([NH:18][C@H:12]([C@@H:13]([OH:17])[C:14]#[C:15][CH3:16])[CH2:11][NH:10][C:9](=[O:19])[O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:51])[CH:40]=[C:41]([C:43]([F:44])([F:45])[F:46])[CH:42]=1)=[O:35])([CH3:32])([CH3:30])[CH3:31]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 211117883-(3-(Tert-butoxycarbonyl)amino-5-(trifluoromethyl)phenylamino)-3-oxopropanoic acidHCID 69196343(2S,3S)-2-amino-3-hydroxy-hex-4-ynyl-carbamic acid benzyl ester

Product 1

HCID 86596719benzyl (2S,3S)-2-(3-(3-(tert-butoxycarbonyl)amino-5-(trifluoromethyl)phenylamino)-3-oxopropanamido)-3-hydroxyhex-4-ynylcarbamateYield 23.4%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

A solution of (2S, 3S)-(2-amino-3-hydroxy-hex-4-ynyl)-carbamic acid benzyl ester (225 mg, prepared as in WO PCT 0250019) in 3:1 CH2Cl2/DMF (12 mL) was charged successively with N,N-diisopropylethylamine (0.54 mL), 3-(3-(tert-butoxycarbonyl)amino-5-(trifluoromethyl)phenylamino)-3-oxopropanoic acid 235 mg), and HATU (283 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-(3-(3-(tert-butoxycarbonyl)amino-5-(trifluoromethyl)phenylamino)-3-oxopropanamido)-3-hydroxyhex-4-ynylcarbamate (92 mg). MS found: (M+Na)+=629.4.

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-42c340ef7a614574aed9f0023aa003f2
Source dataset
uspto-grants-2008_01
Patent number
US07317019B2

Reaction notes

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