Methylamine → (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-3-[(1,3-benzodioxol-5-ylsulfonyl)(isobutyl)amino]-2-hydroxy-1-{4-[4-(methylamino)-4-oxobutoxy]benzyl}propylcarbamate

HRID 1815548Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1815548
[O:1]1[C@H:5]2[O:6][CH2:7][CH2:8][C@H:4]2[C@@H:3]([O:9][C:10]([NH:12][C@H:13]([C@H:28]([OH:47])[CH2:29][N:30]([S:35]([C:38]2[CH:46]=[CH:45][C:41]3[O:42][CH2:43][O:44][C:40]=3[CH:39]=2)(=[O:37])=[O:36])[CH2:31][CH:32]([CH3:34])[CH3:33])[CH2:14][C:15]2[CH:27]=[CH:26][C:18]([O:19][CH2:20][CH2:21][CH2:22][C:23]([OH:25])=O)=[CH:17][CH:16]=2)=[O:11])[CH2:2]1.[CH:48]([N:51](CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.CN>CN(C=O)C.CCO>[O:42]1[C:41]2[CH:45]=[CH:46][C:38]([S:35]([N:30]([CH2:31][CH:32]([CH3:33])[CH3:34])[CH2:29][C@@H:28]([OH:47])[C@@H:13]([NH:12][C:10](=[O:11])[O:9][C@@H:3]3[C@H:4]4[C@H:5]([O:6][CH2:7][CH2:8]4)[O:1][CH2:2]3)[CH2:14][C:15]3[CH:16]=[CH:17][C:18]([O:19][CH2:20][CH2:21][CH2:22][C:23]([NH:51][CH3:48])=[O:25])=[CH:26][CH:27]=3)(=[O:36])=[O:37])=[CH:39][C:40]=2[O:44][CH2:43]1

Komponenten

7

Edukt 4

HCID 6329MethylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57945104HCID 57945104, Verbindung

Produkt 1

HCID 60097292(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-3-[(1,3-benzodioxol-5-ylsulfonyl)(isobutyl)amino]-2-hydroxy-1-{4-[4-(methylamino)-4-oxobutoxy]benzyl}propylcarbamateAusbeute 61,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 702EthanolLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A solution of 35 mg (0.052 mmol) of 4-(4-{(2S,3R)-2-({[(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yloxy]carbonyl}amino)-4-[(1,3-benzodioxol-5-ylsulfonyl)(isobutyl)amino]-3-hydroxybutyl}phenoxy)butanoic acid and 27 μL (0.16 mmol) of N,N-diisopropylethylamine in 1 mL of anhydrous DMF was treated with 49 mg (0.13 mmol) of O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU). The resulting solution was stirred at RT for 15 minutes and was then treated with 0.5 mL of 8M MeNH2 in EtOH. After 18 hours TLC indicated the reaction to be complete. The solution was concentrated to dryness at reduced pressure and the residue subjected to flash chromatography (SiO2, 95:5 CH2Cl2/MeOH) to afford 22 mg (61%) of the desired compound as a white powder. 1H NMR (CDCl3): 7.37 (d, 1H), 7.22 (s, 1H), 7.13 (d, 2H), 6.92 (d, 1H), 6.82 (d, 2H), 6.13 (s, 2H), 5.67 (m, 2H), 5.05 (m, 2H), 4.00 (m, 3H), 3.88 (m, 3H), 3.72 (m, 2H), 3.24-2.71 (m, 11H), 2.40 (t, 2H), 2.16 (m, 2H), 1.88 (m, 1H), 1.67 (m, 1H), 1.53 (m, 1H), 0.94 (m, 6H). MS(ESI): 692(M+H).

Aufarbeitung

  1. waitAfter 18 hours TLC indicated
  2. customthe reaction
  3. concentrationThe solution was concentrated to dryness at reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-a76894348fc04a788a66d16f3b6062ca
Quelldatensatz
uspto-grants-2005_04
Patentnummer
US06878728B1

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