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 1725201Notes

Reaction equation

HRID 1725201 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(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

7

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 1

HCID 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 acctonitrile 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-aa7a3997f77a455ea85879615c1ca0b8
Source dataset
uspto-grants-2009_02
Patent number
US07488848B2

Reaction notes

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