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

HRID 1943214Notes

Reaction equation

HRID 1943214 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:37]2[CH:38]=[CH:39][C:40]([CH:42]=O)=[CH:41][C:36]=2[O:35][CH2:34][CH2:33]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>C(Cl)(Cl)Cl.CO>[ClH:1].[O:32]1[C:37]2[CH:38]=[CH:39][C:40]([CH2:42][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:41][C:36]=2[O:35][CH2:34][CH2:33]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 2481272,3-Dihydro-1,4-benzodioxin-6-carbaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydride2×HCID 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 68598653(1R)-1-({4-[(2,3-Dihydro-1,4-benzodioxin-6-ylmethyl)amino]-1-piperidinyl}methyl)-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione hydrochloride

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

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 (for a preparation see Example 5A(j)) (60 mg, 0.161 mmol) in chloroform (2 ml) and methanol (0.100 ml) at rt under argon was treated with triethylamine (0.067 ml, 0.482 mmol) and stirred at rt for 15 h. The solution was then treated with 2,3-dihydro-1,4-benzodioxin-6-carbaldehyde (commercially available) (23.75 mg, 0.145 mmol) and stirred for a further 30 min. The solution was then treated with sodium triacetoxyborohydride (102 mg, 0.482 mmol) and stirred at rt for 30 min, LC-MS after 30 min showed some starting material present, more sodium triacetoxyborohydride (19 mg) was added, the reaction was stirred for 15 min. This was then treated with saturated aqueous NaHCO3 (10 ml) and extracted with 20% methanol/DCM (3×25 ml). The combined organic extracts were dried (MgSO4), filtered, evaporated and chromatographed (0-20% methanol/DCM) to give the title compound as the free base (48 mg, 67%) as a yellow gum.

Workup

  1. stirringstirred for a further 30 min
  2. stirringstirred at rt for 30 min
  3. waitLC-MS after 30 min showed
  4. stirringthe reaction was stirred for 15 min
  5. extractionextracted with 20% methanol/DCM (3×25 ml)
  6. dry with materialThe combined organic extracts were dried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. customchromatographed (0-20% methanol/DCM)

Sources & evidence

ORD record
ord-82748e65a0e6420488a2f229cc56b68f
Source dataset
uspto-grants-2013_03
Patent number
US08389524B2

Reaction notes

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