Chloroform → 2-({4-[(2,3-Dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}methyl)-1,2-dihydro-3h,8h-2a,5,8a-triazaacenaphthylene-3,8-dione hydrochloride

HRID 1943200Notes

Reaction equation

HRID 1943200 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH:9]2[N:19]3[C:20]4[N:11]([C:12](=[O:22])[CH:13]=[CH:14][C:15]=4[N:16]=[CH:17][C:18]3=[O:21])[CH2:10]2)[CH2:4][CH2:3]1.C(Cl)(Cl)[Cl:24].[O:27]1[C:36]2[CH:35]=[C:34]([CH:37]=O)[N:33]=[CH:32][C:31]=2[O:30][CH2:29][CH2:28]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[ClH:24].[O:27]1[C:36]2[CH:35]=[C:34]([CH2:37][NH:1][CH:2]3[CH2:7][CH2:6][N:5]([CH2:8][CH:9]4[N:19]5[C:20]6[N:11]([C:12](=[O:22])[CH:13]=[CH:14][C:15]=6[N:16]=[CH:17][C:18]5=[O:21])[CH2:10]4)[CH2:4][CH2:3]3)[N:33]=[CH:32][C:31]=2[O:30][CH2:29][CH2:28]1

Participants

6

Reactant 4

HCID 6212ChloroformHCID 5049666Sodium triacetoxyborohydrideHCID 218736682,3-Dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehydeHCID 580017682-((4-aminopiperidin-1-yl)methyl)-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dione

Product 1

HCID 685974202-({4-[(2,3-Dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}methyl)-1,2-dihydro-3h,8h-2a,5,8a-triazaacenaphthylene-3,8-dione hydrochlorideYield 40%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Racemic 2-[(4-amino-1-piperidinyl)methyl]-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dione (for a preparation see Example 16A(j)) (50 mg, 0.166 mmol) was stirred in 9:1 v:v chloroform:methanol (2 ml) with 2,3-dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehyde (for a synthesis see WO2004058144 Example 2(c) or WO03/087098 Example 19(d)) (28 mg, 1.0 equivalent) at room temperature for 30 minutes, then the mixture was treated with sodium triacetoxyborohydride (105 mg, 3.0 equivalents) with vigorous stirring. After a further 25 minutes stirring, the reaction was quenched by addition of saturated aqueous sodium hydrogen carbonate (2 ml), diluted with dichloromethane and stirred vigorously at room temperature for 20 minutes. The organic phase was separated (hydrophobic fit) and evaporated under reduced pressure to give an orange gum; this was purified by column chromatography on silica (eluting with 0-12% (2M NH3 in MeOH) in DCM). Appropriate fractions were combined and evaporated under reduced pressure to give the free base of the title compound as a cream amorphous solid (30 mg, 40%).

Workup

  1. customat room temperature
  2. customfor 30 minutes
  3. stirringAfter a further 25 minutes stirring
  4. customthe reaction was quenched by addition of saturated aqueous sodium hydrogen carbonate (2 ml)
  5. additiondiluted with dichloromethane
  6. stirringstirred vigorously at room temperature for 20 minutes
  7. customThe organic phase was separated (hydrophobic fit)
  8. customevaporated under reduced pressure
  9. customto give an orange gum
  10. customthis was purified by column chromatography on silica (eluting with 0-12% (2M NH3 in MeOH) in DCM)
  11. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-77dff1a096614335937e04781b853e6f
Source dataset
uspto-grants-2013_03
Patent number
US08389524B2

Reaction notes

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