4-Methylmorpholine → (1S,3aR,6aS)-ethyl 2-(2-(3-cyclohexyl-1,1,1-trifluoro-3-(pyrazine-2-carboxamido)propan-2-ylamino)-3,3-dimethylbutanoyl)octahydrocyclopenta[c]pyrrole-1-carboxylate

HRID 424971Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 424971
[CH:1]1([CH:7]([NH:22][C:23]([C:25]2[CH:30]=[N:29][CH:28]=[CH:27][N:26]=2)=[O:24])[CH:8]([NH:13][CH:14]([C:18]([CH3:21])([CH3:20])[CH3:19])[C:15](O)=[O:16])[C:9]([F:12])([F:11])[F:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[C@@H:32]1([C:40]([O:42][CH2:43][CH3:44])=[O:41])[C@H:36]2[CH2:37][CH2:38][CH2:39][C@H:35]2[CH2:34][NH:33]1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O.O1CCCC1.C(OCC)(=O)C>[CH:1]1([CH:7]([NH:22][C:23]([C:25]2[CH:30]=[N:29][CH:28]=[CH:27][N:26]=2)=[O:24])[CH:8]([NH:13][CH:14]([C:18]([CH3:21])([CH3:20])[CH3:19])[C:15]([N:33]2[CH2:34][C@@H:35]3[CH2:39][CH2:38][CH2:37][C@@H:36]3[C@H:32]2[C:40]([O:42][CH2:43][CH3:44])=[O:41])=[O:16])[C:9]([F:10])([F:11])[F:12])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Komponenten

8

Edukt 4

HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 667048352-(3-Cyclohexyl-1,1,1-trifluoro-3-(pyrazine-2-carboxamido)propan-2-ylamino)-3,3-dimethylbutanoic acidHCID 72183111ethyl (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylate hydrochloride

Produkt 1

HCID 86635382(1S,3aR,6aS)-ethyl 2-(2-(3-cyclohexyl-1,1,1-trifluoro-3-(pyrazine-2-carboxamido)propan-2-ylamino)-3,3-dimethylbutanoyl)octahydrocyclopenta[c]pyrrole-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

The stereoisomer of 2-(3-cyclohexyl-1,1,1-trifluoro-3-(pyrazine-2-carboxamido)propan-2-ylamino)-3,3-dimethylbutanoic acid designated as 8A1-isomerA (crude product from above), (1S,3aR,6aS)-ethyl octahydrocyclopenta[c]pyrrole-1-carboxylate (9) (1 eq), N-methylmorpholine (0.106 mL, 2.5 eq) and O-(7-azabenzotriazole-1-yl)-N,N,N,N′-tetramethyluronium hexafluorophosphate (101 mgm, 1 eq) in a mixture of N,N-dimethylformamide (1.2 mL) and tetrahydrofuran (0.2 mL) was stirred at room temperature for 18 hours. The reaction mixture was then diluted with ethyl acetate and washed successively with 1N hydrochloric acid, water, brine and then dried over anhydrous sodium sulfate. Evaporation to dryness under reduced pressure gave crude product, which was purified by silica gel column chromatography. Elution with a solvent gradient from hexane to 20% ethyl acetate/hexane gave pure (1S,3aR,6aS)-ethyl 2-(2-(3-cyclohexyl-1,1,1-trifluoro-3-(pyrazine-2-carboxamido)propan-2-ylamino)-3,3-dimethylbutanoyl)octahydrocyclopenta-[c]pyrrole-1-carboxylate, designated as 10A1-isomer A.

Aufarbeitung

  1. washwashed successively with 1N hydrochloric acid, water, brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. customEvaporation to dryness under reduced pressure
  4. customgave crude product, which
  5. customwas purified by silica gel column chromatography
  6. washElution with a solvent gradient from hexane to 20% ethyl acetate/hexane

Quellen und Nachweise

ORD-Eintrag
ord-cc2e82c7a2ea4407831ebb356d707049
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08106059B2

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