Diisopropylethylamine → (1S,3S,4R)-tert-butyl 3-(1-amino-6-bromonaphthalen-2-ylcarbamoyl)-2-azabicyclo[2.2.1]heptane-2-carboxylate

HRID 1751613Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1751613
[Br:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([NH2:13])[C:8]=2[NH2:12])[CH:3]=1.[C:14]([O:18][C:19]([N:21]1[C@H:26]([C:27](O)=[O:28])[C@H:25]2[CH2:30][C@@H:22]1[CH2:23][CH2:24]2)=[O:20])([CH3:17])([CH3:16])[CH3:15].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[NH2:12][C:8]1[C:9]2[C:4](=[CH:3][C:2]([Br:1])=[CH:11][CH:10]=2)[CH:5]=[CH:6][C:7]=1[NH:13][C:27]([C@@H:26]1[C@H:25]2[CH2:30][C@H:22]([CH2:23][CH2:24]2)[N:21]1[C:19]([O:18][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:20])=[O:28]

Komponenten

6

Edukt 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 220970716-Bromonaphthalene-1,2-diamineHCID 69134534rac-(1R,3R,4S)-2-[(tert-butoxy)carbonyl]-2-azabicyclo[2.2.1]heptane-3-carboxylic acid

Produkt 1

HCID 86708790(1S,3S,4R)-tert-butyl 3-(1-amino-6-bromonaphthalen-2-ylcarbamoyl)-2-azabicyclo[2.2.1]heptane-2-carboxylateAusbeute 95,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of 6-bromonaphthalene-1,2-diamine (1.08 g, 4.56 mmol), and (1S,3S,4R)-2-(tert-butoxycarbonyl)-2-azabicyclo[2.2.1]heptane-3-carboxylic acid (1.10 g, 4.56 mmol) and HATU (2.08 g, 5.47 mmol) in methylene chloride (45 mL) was added DIPEA (3.98 mL, 22.79 mmol). The mixture was stirred at room temperature for two hours. Upon completion, the reaction was concentrated in vacuo, diluted with ethyl acetate and washed with water. The aqueous layer was back extracted with ethyl acetate twice. The combined organic layers were washed with brine, concentrated, and purified by normal phase chromatography (30-80% ethyl acetate (5% MeOH) in hexanes) to give (1S,3S,4R)-tert-butyl 3-(1-amino-6-bromonaphthalen-2-ylcarbamoyl)-2-azabicyclo[2.2.1]heptane-2-carboxylate (2.01 g, 95%). LCMS-ESI+: calc'd for C22H26BrN3O3: 459.12 (M+); Found: 460.9 (M+H+).

Aufarbeitung

  1. concentrationUpon completion, the reaction was concentrated in vacuo
  2. additiondiluted with ethyl acetate
  3. washwashed with water
  4. extractionThe aqueous layer was back extracted with ethyl acetate twice
  5. washThe combined organic layers were washed with brine
  6. concentrationconcentrated
  7. custompurified by normal phase chromatography (30-80% ethyl acetate (5% MeOH) in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-7fd4bacfec5141c3a8a34c869445b631
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09156823B2

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