Triethylamine → (1R)-1-({4-[(6,7-Dihydro-5H-cyclopenta[c]pyridin-3-ylmethyl)amino]-1-piperidinyl}methyl)-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione hydrochloride

HRID 1943164Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1943164
[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[CH:18]=[CH:19][C:20]3=[O:23])[CH2:12]2)[CH2:6][CH2:5]1.C(N(CC)CC)C.[CH:32]1[C:37]2[CH2:38][CH2:39][CH2:40][C:36]=2[CH:35]=[C:34]([CH:41]=O)[N:33]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+]>C(Cl)(Cl)Cl.CO>[ClH:1].[CH:32]1[C:37]2[CH2:38][CH2:39][CH2:40][C:36]=2[CH:35]=[C:34]([CH2:41][NH:3][CH:4]2[CH2:5][CH2:6][N:7]([CH2:10][C@H:11]3[N:21]4[C:22]5[N:13]([C:14](=[O:24])[CH:15]=[CH:16][C:17]=5[CH:18]=[CH:19][C:20]4=[O:23])[CH2:12]3)[CH2:8][CH2:9]2)[N:33]=1

Komponenten

8

Edukt 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 66658412(1R)-1-[(4-amino-1-piperidinyl)methyl]-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione dihydrochlorideHCID 866420966,7-Dihydro-5H-cyclopenta[c]pyridine-3-carbaldehyde

Produkt 1

HCID 68597793(1R)-1-({4-[(6,7-Dihydro-5H-cyclopenta[c]pyridin-3-ylmethyl)amino]-1-piperidinyl}methyl)-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione hydrochlorideAusbeute 41 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6212ChloroformLösungsmittel

Versuchsvorschrift

A suspension of (1R)-1-[(4-amino-1-piperidinyl)methyl]-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione dihydrochloride (82 mg, 0.220 mmol) (for a preparation see Example 5(j)) in chloroform (5 ml) and methanol (0.2 ml) at rt under argon was treated with triethylamine (92 μl, 0.659 mmol) and stirred at rt for 0.25 h. The solution was then treated with 6,7-dihydro-5H-cyclopenta[c]pyridine-3-carbaldehyde (32.3 mg, 0.220 mmol) and stirred for a further 0.5 h. The solution was then treated with NaBH(OAc)3 (140 mg, 0.659 mmol) and stirred at rt for 0.5 h. The reaction was then treated with saturated aqueous NaHCO3 (100 ml) and extracted with 20% methanol/DCM (3×200 ml). The combined organic extracts were dried (MgSO4), filtered, evaporated and chromatographed (0-20% methanol/DCM) to give the free base of the title compound as a light brown solid (39 mg, 41%).

Aufarbeitung

  1. stirringstirred for a further 0.5 h
  2. stirringstirred at rt for 0.5 h
  3. extractionextracted with 20% methanol/DCM (3×200 ml)
  4. dry with materialThe combined organic extracts were dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customchromatographed (0-20% methanol/DCM)

Quellen und Nachweise

ORD-Eintrag
ord-cce975f95a7c4eaaa8be183fe2330409
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08389524B2

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