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 1943235Notes

Reaction equation

HRID 1943235 reaction equation
[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

Participants

6

Reactant 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

Product 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 hydrochlorideYield 26%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6212ChloroformSolvent2×

Procedure

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%).

Workup

  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

Sources & evidence

ORD record
ord-07954d12bd794a9588c265d122c3dcf0
Source dataset
uspto-grants-2013_03
Patent number
US08389524B2

Reaction notes

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