4-Methylmorpholine → 2-hydroxy-3(S)-{3-(pyridin-3-ylmethanesulfonyl)-2(R)-[2,2,2-trifluoro-1(S)-(4-fluorophenyl)ethylamino]propionylamino} hexanoic acid cyclopropylamide

HRID 1192730Notes

Reaction equation

HRID 1192730 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][S:8]([CH2:11][C@H:12]([NH:16][C@@H:17]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[C:18]([F:21])([F:20])[F:19])[C:13]([OH:15])=O)(=[O:10])=[O:9])[CH:2]=1.[CH:29]1([NH:32][C:33](=[O:41])[CH:34]([OH:40])[C@@H:35]([NH2:39])[CH2:36][CH2:37][CH3:38])[CH2:31][CH2:30]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[NH4+].[Cl-]>C(#N)C.C(OCC)(=O)C>[CH:29]1([NH:32][C:33](=[O:41])[CH:34]([OH:40])[C@@H:35]([NH:39][C:13](=[O:15])[C@@H:12]([NH:16][C@@H:17]([C:22]2[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=2)[C:18]([F:21])([F:20])[F:19])[CH2:11][S:8]([CH2:7][C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)(=[O:9])=[O:10])[CH2:36][CH2:37][CH3:38])[CH2:31][CH2:30]1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 25517Ammonium ChlorideHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 23634853(3S)-3-Amino-N-cyclopropyl-2-hydroxyhexanamideHCID 596090603-(pyridin-3-ylmethanesulfonyl)-2-(R)[2,2,2-trifluoro-1(s)-(4-fluorophenyl)ethylamino]propionic acid

Product 1

HCID 596090592-hydroxy-3(S)-{3-(pyridin-3-ylmethanesulfonyl)-2(R)-[2,2,2-trifluoro-1(S)-(4-fluorophenyl)ethylamino]propionylamino} hexanoic acid cyclopropylamide

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 3-(pyridin-3-ylmethanesulfonyl)-2-(R)[2,2,2-trifluoro-1(S)-(4-fluorophenyl)ethylamino] propionic acid (420 mg, 1 mmol), 3(S)-amino-2-hydroxyhexanoic acid cyclopropylamide (186 mg, 1 mmol) prepared as described in PCT application publication No. WO-02/18369 as compound xiii, HBTU (455 mg, 1.2 mmol), and NMM (0.44 mL, 4 mmol) in acetonitrile was stirred at room temperature overnight. Sat. NH4Cl (10 mL) and ethyl acetate (10 mL) were added and after 20 min the aqueous layer was extracted with ethyl acetate. The combined organic extracts were washed with brine and dried with MgSO4, filtered and the filtrated was concentrated under the reduced pressure to give 2-hydroxy-3(S)-{3-(pyridin-3-ylmethanesulfonyl)-2(R)[2,2,2-trifluoro-1(S)-(4-fluorophenyl)-ethylamino]propionylamino}-hexanoic acid cyclopropylamide which was used in the next step without further purification.

Workup

  1. customprepared
  2. extractionwas extracted with ethyl acetate
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried with MgSO4
  5. filtrationfiltered
  6. concentrationthe filtrated was concentrated under the reduced pressure

Sources & evidence

ORD record
ord-ca43744e21734776ad86128a8e278220
Source dataset
uspto-grants-2014_03
Patent number
US08680152B2

Reaction notes

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