Dichloromethane → HCID 68995440, compound

HRID 656991Notes

Reaction equation

HRID 656991 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.[N:23]1[C:28]2[O:29][CH2:30][CH2:31][O:32][C:27]=2[CH:26]=[C:25]([CH:33]=O)[N: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].[N:23]1[C:28]2[O:29][CH2:30][CH2:31][O:32][C:27]=2[CH:26]=[C:25]([CH2:33][NH:1][CH:2]2[CH2:3][CH2:4][N:5]([CH2:8][CH2:9][N:10]3[C:15](=[O:16])[CH:14]=[N:13][C:12]4[CH:17]=[CH:18][C:19]([O:21][CH3:22])=[N:20][C:11]3=4)[CH2:6][CH2:7]2)[N:24]=1

Participants

7

Reactant 5

HCID 6344Dichloromethane2×HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydride2×HCID 248916966,7-Dihydro-[1,4]dioxino[2,3-c]pyridazine-3-carbaldehyde2×HCID 578153944-[2-(4-Aminopiperidin-1-yl)ethyl]-6-methoxypyrido[2,3-b]pyrazin-3(4H)-one

Product 1

HCID 68995440HCID 68995440, compoundYield 35%

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 (50 mg, 0.1648 mmoles) and 6,7-dihydro[1,4]dioxino[2,3-c]pyridazine-3-carbaldehyde (30.1 mg, 0.181 mmoles) in anhydrous DCM (5 ml) and anhydrous MeOH (0.5 ml) was stirred at rt for 5 minutes. Sodium triacetoxyborohydride (115 mg, 0.543 mmoles) was added and the mixture was stirred, under argon, for 24 hours. A further 6,7-dihydro[1,4]dioxino[2,3-c]pyridazine-3-carbaldehyde (15 mg, 0.09 mmoles) and sodium triacetoxyborohydride (50 mg, 0.236 mmoles) were added and reaction was stirred for 5 hours, treated with sat. aq. NaHCO3 solution (2 ml) and 9:1 DCM:MeOH (5 ml). The layers were separated and the aqueous layer was washed with 9:1 DCM:MeOH (10 ml) and 5:1 DCM:MeOH (2×20 ml). The organic extracts were combined, passed through a hydrophobic frit and evaporated to an orange gum. Purification on a 20 g silica column eluted with a 20:1 to 10:1 DCM:MeOH gradient elution gave the free base of the title compound as a pale yellow gum (26.1 mg, 35%)

Workup

  1. customreaction
  2. stirringwas stirred for 5 hours
  3. customThe layers were separated
  4. washthe aqueous layer was washed with 9:1 DCM
  5. customevaporated to an orange gum
  6. customPurification on a 20 g silica column
  7. washeluted with a 20:1 to 10:1 DCM
  8. washMeOH gradient elution

Sources & evidence

ORD record
ord-e42d6d1e09d7428cbda2d8a6175c6837
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

Loading…