Diisopropylethylamine → (2S,3S)-[2-(2-{2-[(azetidine-1-carbonyl)-amino]-5-trifluoromethyl-benzoylamino}-acetylamino)-3-hydroxy-hex-4-ynyl]-carbamic acid benzyl ester

HRID 2250800Notes

Reaction equation

HRID 2250800 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.CCN(C(C)C)C(C)C.[N:29]1([C:33]([NH:35][C:36]2[CH:48]=[CH:47][C:46]([C:49]([F:52])([F:51])[F:50])=[CH:45][C:37]=2[C:38]([NH:40][CH2:41][C:42](O)=[O:43])=[O:39])=[O:34])[CH2:32][CH2:31][CH2:30]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[CH2:1]([O:8][C:9](=[O:19])[NH:10][CH2:11][C@H:12]([NH:18][C:42](=[O:43])[CH2:41][NH:40][C:38](=[O:39])[C:37]1[CH:45]=[C:46]([C:49]([F:51])([F:52])[F:50])[CH:47]=[CH:48][C:36]=1[NH:35][C:33]([N:29]1[CH2:32][CH2:31][CH2:30]1)=[O:34])[C@@H:13]([OH:17])[C:14]#[C:15][CH3:16])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

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 21991185{2-[(Azetidine-1-carbonyl)-amino]-5-trifluoromethyl-benzoylamino}-acetic acidHCID 69196343(2S,3S)-2-amino-3-hydroxy-hex-4-ynyl-carbamic acid benzyl ester

Product 1

HCID 69198306(2S,3S)-[2-(2-{2-[(azetidine-1-carbonyl)-amino]-5-trifluoromethyl-benzoylamino}-acetylamino)-3-hydroxy-hex-4-ynyl]-carbamic acid benzyl esterYield 63.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(2S,3S)-(2-Amino-3-hydroxy-hex-4-ynyl)-carbamic acid benzyl ester (520 mg, prepared as in WO PCT 0250019) was dissolved in CH2Cl2 (20 ml) and DIEA (0.74 ml) and cooled to 0° C. prior to the addition of {2-[(azetidine-1-carbonyl)-amino]-5-trifluoromethyl-benzoylamino}-acetic acid (684 mg, prepared as in WO PCT 0250019) and HATU (756 mg). After the reaction was stirred overnight at room temperature, the CH2Cl2was removed and EtOAc was added. The organic layer was washed with saturated NH4Cl solution (aq) brine, dried, filtered, and concentrated. Flashed chromatography of the resulting residue gave (2S,3S)-[2-(2-{2-[(azetidine-1-carbonyl)-amino]-5-trifluoromethyl-benzoylamino}-acetylamino)-3-hydroxy-hex-4-ynyl]-carbamic acid benzyl ester (745 mg). MS found: (M+H)+=590.

Workup

  1. customthe CH2Cl2was removed
  2. additionEtOAc was added
  3. washThe organic layer was washed with saturated NH4Cl solution (aq) brine
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-34af8b664fca4419a35e62d609dd968c
Source dataset
uspto-grants-2008_01
Patent number
US07317019B2

Reaction notes

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