Dichloromethane → 4-(2-{4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}ethyl)-6-(methyloxy)pyrido[2,3-b]pyrazin-3(4H)-one Dihydrochloride

HRID 656964Notes

Reaction equation

HRID 656964 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][N:10]2[C:15](=[O:16])[CH:14]=[N:13][C:12]3[CH:17]=[CH:18][C:19]([O:21][CH3:22])=[N:20][C:11]2=3)[CH2:4][CH2:3]1.[O:23]1[C:32]2[CH:31]=[C:30]([CH:33]=O)[N:29]=[CH:28][C:27]=2[O:26][CH2:25][CH2:24]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+].C(Cl)[Cl:55]>CO>[ClH:55].[ClH:55].[O:23]1[C:32]2[CH:31]=[C:30]([CH2:33][NH:1][CH:2]3[CH2:3][CH2:4][N:5]([CH2:8][CH2:9][N:10]4[C:15](=[O:16])[CH:14]=[N:13][C:12]5[CH:17]=[CH:18][C:19]([O:21][CH3:22])=[N:20][C:11]4=5)[CH2:6][CH2:7]3)[N:29]=[CH:28][C:27]=2[O:26][CH2:25][CH2:24]1

Participants

7

Reactant 5

HCID 6344Dichloromethane2×HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 218736682,3-Dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehydeHCID 578153944-[2-(4-Aminopiperidin-1-yl)ethyl]-6-methoxypyrido[2,3-b]pyrazin-3(4H)-one

Product 1

HCID 689943954-(2-{4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}ethyl)-6-(methyloxy)pyrido[2,3-b]pyrazin-3(4H)-one DihydrochlorideYield 57%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A solution of 4-[2-(4-amino-1-piperidinyl)ethyl]-6-(methyloxy)pyrido[2,3-b]pyrazin-3(4H)-one (150 mg, 0.494 mmoles) and 2,3-dihydro[1,4]dioxino[2,3-c]pyridine-7-carboxaldehyde (for a synthesis see WO2004058144, Example 2(c) or WO03/087098, Example 19(d)) (82 mg, 0.496 mmoles) in anhydrous DCM (10 ml) and anhydrous MeOH (1 ml) was stirred at rt for 5 minutes. Sodium triacetoxyborohydride (316 mg, 1.49 mmoles) was added and the mixture was stirred, under argon, for 18 h, treated with sat. aq. NaHCO3 solution (5 ml) and 10:1 DCM:MeOH (10 ml). The layers were separated and the aqueous layer was washed with 10:1 DCM:MeOH (5 ml). The organic extracts were combined, washed with brine, passed through a hydrophobic frit and evaporated to an orange gum. Purification on a 20 g silica column eluted with a 0% to 30% DCM/MeOH gradient elution gave the free base of the title compound as a colourless gum (128 mg, 57%).

Workup

  1. customThe layers were separated
  2. washthe aqueous layer was washed with 10:1 DCM
  3. washwashed with brine
  4. customevaporated to an orange gum
  5. customPurification on a 20 g silica column
  6. washeluted with a 0% to 30% DCM/MeOH gradient elution

Sources & evidence

ORD record
ord-31e6dc22350d420e9f4d40656e447d4b
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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