Chloroform → 7-{[(1-{[(2R)-3,8-Dioxo-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylen-2-yl]methyl}-4-piperidinyl)amino]methyl}-2,3-dihydro-1,4-benzodioxin-5-carbonitrile hydrochloride

HRID 1943228Notes

Reaction equation

HRID 1943228 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C@H: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.[CH:23]([C:25]1[CH:26]=[C:27]([C:35]#[N:36])[C:28]2[O:33][CH2:32][CH2:31][O:30][C:29]=2[CH:34]=1)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+].C(Cl)(Cl)[Cl:57]>CO>[ClH:57].[O:21]=[C:18]1[CH:17]=[N:16][C:15]2=[C:20]3[N:19]1[C@H:9]([CH2:8][N:5]1[CH2:6][CH2:7][CH:2]([NH:1][CH2:23][C:25]4[CH:26]=[C:27]([C:35]#[N:36])[C:28]5[O:33][CH2:32][CH2:31][O:30][C:29]=5[CH:34]=4)[CH2:3][CH2:4]1)[CH2:10][N:11]3[C:12](=[O:22])[CH:13]=[CH:14]2

Participants

7

Reactant 5

HCID 6212ChloroformHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 57423114HCID 57423114, compoundHCID 58200877(2R)-2-[(4-Amino-1-piperidinyl)methyl]-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dione

Product 1

HCID 685971587-{[(1-{[(2R)-3,8-Dioxo-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylen-2-yl]methyl}-4-piperidinyl)amino]methyl}-2,3-dihydro-1,4-benzodioxin-5-carbonitrile hydrochlorideYield 42.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A suspension of (2R)-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)) (60 mg, 0.199 mmol) and 7-formyl-2,3-dihydro-1,4-benzodioxin-5-carbonitrile (for a synthesis see WO06014580 Preparation 13 or WO2007122258, Example 31(d)) (37.7 mg, 0.199 mmol) in chloroform (2 ml) and methanol (0.100 ml) at room temperature under nitrogen was treated with sodium triacetoxyborohydride (127 mg, 0.597 mmol) and stirred for 90 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 (NaSO4), filtered, evaporated and purified using silica chromatography (0-20% methanol/DCM) to give the free base of the title compound as a yellow gum (40 mg, 42.3%).

Workup

  1. extractionextracted with 20% methanol/DCM (3×25 ml)
  2. dry with materialThe combined organic extracts were dried (NaSO4)
  3. filtrationfiltered
  4. customevaporated
  5. custompurified

Sources & evidence

ORD record
ord-1570d810b1ee476780e0b5594366d4ac
Source dataset
uspto-grants-2013_03
Patent number
US08389524B2

Reaction notes

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