Sodium triacetoxyborohydride → 2-({4-[([1,3]Oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-1,2-dihydro-3h,8h-2a,5,8a-triazaacenaphthylene-3,8-dione hydrochloride

HRID 1943198Notes

Reaction equation

HRID 1943198 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.[S:23]1[C:31]2[CH:30]=[C:29]([CH:32]=O)[N:28]=[CH:27][C:26]=2[O:25][CH2:24]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(Cl)(Cl)[Cl:49].CO>>[ClH:49].[S:23]1[C:31]2[CH:30]=[C:29]([CH2:32][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:28]=[CH:27][C:26]=2[O:25][CH2:24]1

Participants

5

Reactant 4

HCID 5049666Sodium triacetoxyborohydrideHCID 21584188Chloroform methanolHCID 580017682-((4-aminopiperidin-1-yl)methyl)-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dioneHCID 59254367[1,3]Oxathiolo[5,4-c]pyridine-6-carbaldehyde

Product 1

HCID 685973492-({4-[([1,3]Oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-1,2-dihydro-3h,8h-2a,5,8a-triazaacenaphthylene-3,8-dione hydrochlorideYield 46.8%

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)) (400 mg, 1.327 mmol) was stirred with [1,3]oxathiolo[5,4-c]pyridine-6-carbaldehyde (for a synthesis see WO2004058144 Example 61) (200 mg, 0.9 eq.) in chloroform:methanol (9:1, v:v, 15 ml) at room temperature for 30 mins; the mixture was then treated with sodium triacetoxyborohydride (844 mg, 3.0 eq.) with vigorous stirring at room temperature for 30 mins. The reaction was quenched by addition of saturated aqueous sodium hydrogen carbonate (5 ml) and the mixture was stirred at room temperature for 5 mins. The organic phase was separated, dried over anhydrous Na2SO4 and evaporated under reduced pressure. The crude product was purified by column chromatography on silica (eluting with 0-12% (2M ammonia in methanol) in DCM, appropriate fractions were combined and evaporated under reduced pressure to give the free base of the (racemic) title compound as a pale yellow foam (290 mg, 46.8%).

Workup

  1. customat room temperature
  2. customfor 30 mins
  3. customThe reaction was quenched by addition of saturated aqueous sodium hydrogen carbonate (5 ml)
  4. stirringthe mixture was stirred at room temperature for 5 mins
  5. customThe organic phase was separated
  6. dry with materialdried over anhydrous Na2SO4
  7. customevaporated under reduced pressure
  8. customThe crude product was purified by column chromatography on silica (
  9. washeluting with 0-12% (2M ammonia in methanol) in DCM
  10. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-7a7ee01f15374ee08e5b758aced01a5b
Source dataset
uspto-grants-2013_03
Patent number
US08389524B2

Reaction notes

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