Dichloromethane → HCID 68598594, compound

HRID 1943128Notes

Reaction equation

HRID 1943128 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH:9]2[N:19]3[CH:20]4[CH:15]([CH:16]=[CH:17][C:18]3=[O:21])[N:14]=[CH:13][C:12](=[O:22])[N:11]4[CH2:10]2)[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+].[Cl:54]CCl>CO>[ClH:54].[ClH:54].[O:23]1[C:32]2[CH:31]=[C:30]([CH2:33][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]=[N:14][C:15]=6[CH:16]=[CH:17][C:18]5=[O:21])[CH2:10]4)[CH2:4][CH2:3]3)[N:29]=[CH:28][C:27]=2[O:26][CH2:25][CH2:24]1

Participants

7

Reactant 5

HCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydride2×HCID 218736682,3-Dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehyde2×HCID 67030011HCID 67030011, compound

Product 1

HCID 68598594HCID 68598594, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 1-[(4-amino-1-piperidinyl)methyl]-1,2,5a,8b-tetrahydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dione (22.8 mg, 0.0757 mmol) in anhydrous dichloromethane (3 ml) and anhydrous methanol (0.6 ml) was treated with 2,3-dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehyde (12.5 mg, 0.076 mmol) (for a synthesis see WO2004058144 Example 2(c) or WO03/087098 Example 19(d)) and stirred, under argon, for 15 minutes and then treated with sodium triacetoxyborohydride (48 mg, 0.226 mmol) and stirred at room temperature for 17 hours. The reaction was then treated with a further portion of 2,3-dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehyde (2 mg) and sodium triacetoxyborohydride (10 mg) and the mixture was stirred for 4 hours, treated with saturated aqueous NaHCO3 solution (1 ml) and stirred for 10 minutes. The layers were separated and the aqueous layer was washed with 9:1 dichloromethane:methanol (2×10 ml). The combined organic extracts were passed through a hydrophobic frit and evaporated to a brown gum which was chromatographed eluting with 0 to 30% methanol in dichloromethane to give the free base of the title compound as a yellow gum (20.6 mg, 60%).

Workup

  1. stirringstirred at room temperature for 17 hours
  2. stirringthe mixture was stirred for 4 hours
  3. stirringstirred for 10 minutes
  4. customThe layers were separated
  5. washthe aqueous layer was washed with 9:1 dichloromethane
  6. customevaporated to a brown gum which
  7. customwas chromatographed
  8. washeluting with 0 to 30% methanol in dichloromethane

Sources & evidence

ORD record
ord-266c86d775094e2e8eecd6ceb6427e50
Source dataset
uspto-grants-2013_03
Patent number
US08389524B2

Reaction notes

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