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

HRID 1943235Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1943235
[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.[O:32]1[C:36]2[CH:37]=[C:38]([CH:41]=O)[CH:39]=[CH:40][C:35]=2[CH2:34][CH2:33]1>C(Cl)(Cl)Cl.CO>[ClH:1].[O:32]1[C:36]2[CH:37]=[C:38]([CH2:41][NH:3][CH:4]3[CH2:5][CH2:6][N:7]([CH2:10][C@H:11]4[N:21]5[C:22]6[N:13]([C:14](=[O:24])[CH:15]=[CH:16][C:17]=6[CH:18]=[CH:19][C:20]5=[O:23])[CH2:12]4)[CH2:8][CH2:9]3)[CH:39]=[CH:40][C:35]=2[CH2:34][CH2:33]1

Komponenten

6

Edukt 3

HCID 8471TriethylamineHCID 149643942,3-Dihydrobenzofuran-6-carbaldehydeHCID 66658412(1R)-1-[(4-amino-1-piperidinyl)methyl]-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione dihydrochloride

Produkt 1

HCID 68598338(1R)-1-({4-[(2,3-Dihydro-1-benzofuran-6-ylmethyl)amino]-1-piperidinyl}methyl)-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione hydrochlorideAusbeute 26 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6212ChloroformLösungsmittel2×

Versuchsvorschrift

A solution 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 (for a preparation see Example 5A(j)) (133 mg, 0.356 mmol) and triethylamine (0.124 ml, 0.891 mmol) in chloroform (4.5 ml) and methanol (0.5 ml) at rt was stirred at rt for 15 min then 2,3-dihydro-1-benzofuran-6-carbaldehyde (44 mg, 0.297 mmol) in chloroform (2 ml) was added dropwise at rt. The reaction mixture was stirred at rt overnight. The reaction was quenched with NaHCO3 (aq) (20 ml), extracted with 20% MeOH/DCM (3×30 ml). The combined organic layers were dried over MgSO4, filtered, evaporated and chromatographed (0-50% MeOH/DCM). The relevant fractions were combined and evaporated to deliver the free base of the title compound as a pale yellow clear oil (18 mg, 0.04 mmol, 26%).

Aufarbeitung

  1. customat rt
  2. stirringThe reaction mixture was stirred at rt overnight
  3. customThe reaction was quenched with NaHCO3 (aq) (20 ml)
  4. extractionextracted with 20% MeOH/DCM (3×30 ml)
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customchromatographed (0-50% MeOH/DCM)
  9. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-07954d12bd794a9588c265d122c3dcf0
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08389524B2

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