Triethylamine → (2R)-2-[(4-{[(5-Fluoro-2,3-dihydro-1,4-benzodioxin-6-yl)methyl]amino}-1-piperidinyl)methyl]-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dione hydrochloride

HRID 1943239Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1943239
[ClH:1].Cl.[NH2:3][CH:4]1[CH2:9][CH2:8][N:7]([CH2:10][C@H:11]2[N:21]3[C:22]4[N:13]([C:14](=[O:24])[CH:15]=[CH:16][C:17]=4[N:18]=[CH:19][C:20]3=[O:23])[CH2:12]2)[CH2:6][CH2:5]1.C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl.C(N(CC)CC)C.[F:46][C:47]1[C:56]2[O:55][CH2:54][CH2:53][O:52][C:51]=2[CH:50]=[CH:49][C:48]=1[CH:57]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>CO>[ClH:1].[F:46][C:47]1[C:56]2[O:55][CH2:54][CH2:53][O:52][C:51]=2[CH:50]=[CH:49][C:48]=1[CH2:57][NH:3][CH:4]1[CH2:9][CH2:8][N:7]([CH2:10][C@H:11]2[N:21]3[C:22]4[N:13]([C:14](=[O:24])[CH:15]=[CH:16][C:17]=4[N:18]=[CH:19][C:20]3=[O:23])[CH2:12]2)[CH2:6][CH2:5]1

Komponenten

8

Edukt 6

HCID 8471TriethylamineHCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydride2×HCID 68598038(2R)-2-[(4-amino-1-piperidinyl)methyl]-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dione dihydrochlorideHCID 866421125-Fluoro-2,3-dihydro-1,4-benzodioxin-6-carbaldehyde

Produkt 1

HCID 68597997(2R)-2-[(4-{[(5-Fluoro-2,3-dihydro-1,4-benzodioxin-6-yl)methyl]amino}-1-piperidinyl)methyl]-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dione hydrochlorideAusbeute 45 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

A suspension of (2R)-2-[(4-amino-1-piperidinyl)methyl]-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dione dihydrochloride (for a preparation see Example 16A(j), amine was converted into dihydrochloride after chiral hplc purification) (51.3 mg, 0.137 mmol) in chloroform (5 ml) and methanol (0.1 ml) at rt under argon was treated with triethylamine (0.057 ml, 0.411 mmol) and stirred at rt for 0.25 h. The solution was then treated with 5-fluoro-2,3-dihydro-1,4-benzodioxin-6-carbaldehyde (24.95 mg, 0.137 mmol) and stirred for a further 0.5 h. The solution was then treated with sodium triacetoxyborohydride (174 mg, 0.822 mmol) and stirred at rt for 2 h, more sodium triacetoxyborohydride (174 mg, 0.137 mmol) was added, reaction stirred for a further 1 h, the reaction was then treated with saturated aqueous NaHCO3 (20 ml) and extracted with 20% methanol/DCM (3×20 ml). The combined organic extracts were dried (MgSO4) and chromatographed (0-20% methanol:DCM) to give the free base of the title compound as a white solid (29 mg, 0.062 mmol, 45%,).

Aufarbeitung

  1. customafter chiral hplc purification) (51.3 mg, 0.137 mmol) in chloroform (5 ml)
  2. stirringstirred for a further 0.5 h
  3. stirringstirred at rt for 2 h
  4. customreaction
  5. stirringstirred for a further 1 h
  6. extractionextracted with 20% methanol/DCM (3×20 ml)
  7. dry with materialThe combined organic extracts were dried (MgSO4)
  8. customchromatographed (0-20% methanol:DCM)

Quellen und Nachweise

ORD-Eintrag
ord-5f3b45cbe75a404e871a286cbed17285
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08389524B2

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