4-Methylmorpholine → tert-butyl (2S)-1-((1S,3aR,6aS)-1-((3S)-1-(cyclopropylamino)-2-hydroxy-1-oxohexan-3-ylcarbamoyl)hexahydrocyclopenta-[c]pyrrol-2(1H)-yl)-3,3-dimethyl-1-oxobutan-2-ylcarbamate

HRID 424973Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 424973
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C:23]([CH3:26])([CH3:25])[CH3:24])[C:10]([N:12]1[CH2:16][C@@H:15]2[CH2:17][CH2:18][CH2:19][C@@H:14]2[C@H:13]1[C:20](O)=[O:21])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.CN1CCOCC1.[NH2:55][C@@H:56]([CH2:65][CH2:66][CH3:67])[CH:57]([OH:64])[C:58]([NH:60][CH:61]1[CH2:63][CH2:62]1)=[O:59].Cl.N[C@@H](CCC)C(O)C(NC1CC1)=O>ClCCl.CN(C)C=O.O>[CH:61]1([NH:60][C:58](=[O:59])[CH:57]([OH:64])[C@@H:56]([NH:55][C:20]([C@@H:13]2[C@H:14]3[CH2:19][CH2:18][CH2:17][C@H:15]3[CH2:16][N:12]2[C:10](=[O:11])[C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3])[C:23]([CH3:24])([CH3:26])[CH3:25])=[O:21])[CH2:65][CH2:66][CH3:67])[CH2:63][CH2:62]1

Komponenten

10

Edukt 6

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 23634853(3S)-3-Amino-N-cyclopropyl-2-hydroxyhexanamideHCID 59677749(1S,3aR,6aS)-2-((S)-2-(tert-butoxycarbonylamino)-3,3-dimethylbutanoyl)octahydrocyclopenta[c]pyrrole-1-carboxylic acidHCID 66656935Hexanamide, 3-amino-N-cyclopropyl-2-hydroxy-, hydrochloride (1:1), (3S)-

Produkt 1

HCID 57930532tert-butyl (2S)-1-((1S,3aR,6aS)-1-((3S)-1-(cyclopropylamino)-2-hydroxy-1-oxohexan-3-ylcarbamoyl)hexahydrocyclopenta-[c]pyrrol-2(1H)-yl)-3,3-dimethyl-1-oxobutan-2-ylcarbamate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

The crude (1S,3aR,6aS)-2-((S)-2-(tert-butoxycarbonylamino)-3,3-dimethylbutanoyl)octahydrocyclopenta[c]pyrrole-1-carboxylic acid from Example 10 was dissolved in dichloromethane (4 mL) and treated with 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide (EDCI) (71 mg, 2 eq), 1-hydroxybenzotriazole (HOBT) (57 mg, 2 eq) and N-methyl morpholine (0.2 mL, 5 eq) at room temperature. To this mixture was added after 30 minutes (3S)-3-amino-N-cyclopropyl-2-hydroxyhexanamide, the compound of formula (12) (1 eq) in dichloromethane (3 mL) and N,N-dimethylformamide (3 mL) and the reaction mixture was stirred at room temperature. After 18 hours the reaction mixture was diluted with water, and the product extracted into ethyl acetate. The organic extract was washed with brine, dried and evaporated to dryness under reduced pressure, to give crude tert-butyl (2S)-1-((1S,3aR,6aS)-1-((3S)-1-(cyclopropylamino)-2-hydroxy-1-oxohexan-3-ylcarbamoyl)hexahydrocyclopenta-[c]pyrrol-2(1H)-yl)-3,3-dimethyl-1-oxobutan-2-ylcarbamate, the compound of formula (17).

Aufarbeitung

  1. extractionthe product extracted into ethyl acetate
  2. extractionThe organic extract
  3. washwas washed with brine
  4. customdried
  5. customevaporated to dryness under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-9396a053a37e483d8d6635c38edf50fa
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08106059B2

Notizen zur Reaktion

Wird geladen…