Dichloromethane → (2R)-2-[(4-{[(3-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dione hydrochloride

HRID 1943213Notes

Reaction equation

HRID 1943213 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.[O:23]=[C:24]1[CH2:29][S:28][C:27]2[CH:30]=[CH:31][C:32]([CH:34]=O)=[N:33][C:26]=2[NH:25]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+].C(Cl)[Cl:56]>CO.C(Cl)(Cl)Cl>[ClH:56].[O:23]=[C:24]1[CH2:29][S:28][C:27]2[CH:30]=[CH:31][C:32]([CH2:34][NH:1][CH:2]3[CH2:7][CH2:6][N:5]([CH2:8][C@H: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:33][C:26]=2[NH:25]1

Participants

8

Reactant 5

HCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 115935913-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehydeHCID 58200877(2R)-2-[(4-Amino-1-piperidinyl)methyl]-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dione

Product 1

HCID 68596274(2R)-2-[(4-{[(3-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dione hydrochloride

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

(2R)-2-[(4-Amino-1-piperidinyl)methyl]-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dione (50 mg, 0.166 mmol) (for a preparation see Example 16(j)) and 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carboxaldehyde (29 mg, 0.90 eq.) (for a synthesis see WO2003087098, Example 301(d)) were stirred in 9:1 chloroform:methanol (1 ml) at room temperature for 3 hours, then sodium triacetoxyborohydride (105 mg, 3.00 eq.) was added. The mixture was stirred at room temperature for a further 30 minutes, then saturated aqueous sodium hydrogen carbonate (0.5 ml) was added, and the organic phase was diluted with DCM (10 ml). The mixture was stirred vigorously for 10 minutes, then the organic phase was separated (hydrophobic frit) and evaporated under reduced pressure. The residue was taken up in DCM (ca. 3 ml)+1 drop MeOH and purified by column chromatography on silica (eluted with 0-12% (2M NH3 in MeOH) in DCM). Appropriate fractions were combined and evaporated to give the free base of the title compound as a yellow amorphous solid.

Workup

  1. stirringThe mixture was stirred vigorously for 10 minutes
  2. customthe organic phase was separated (hydrophobic frit)
  3. customevaporated under reduced pressure
  4. custompurified by column chromatography on silica (eluted with 0-12% (2M NH3 in MeOH) in DCM)
  5. customevaporated

Sources & evidence

ORD record
ord-40a7d2efb9aa407d980e3cd3cc3f7861
Source dataset
uspto-grants-2013_03
Patent number
US08389524B2

Reaction notes

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