Dichloromethane → (2R)-2-({4-[(3,4-Dihydro-2H-[1,4]oxathiepino[2,3-c]pyridin-8-ylmethyl)amino]-1-piperidinyl}methyl)-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dione hydrochloride

HRID 1943211Notes

Reaction equation

HRID 1943211 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.[S:23]1[C:33]2[CH:32]=[C:31]([CH:34]=O)[N:30]=[CH:29][C:28]=2[O:27][CH2:26][CH2:25][CH2:24]1.S1C2C=C(C=O)N=CC=2OCC1.BrC(Br)(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+].[Cl:72]CCl>CO.C(Cl)(Cl)Cl>[ClH:72].[S:23]1[C:33]2[CH:32]=[C:31]([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:30]=[CH:29][C:28]=2[O:27][CH2:26][CH2:25][CH2:24]1

Participants

10

Reactant 7

HCID 6344DichloromethaneHCID 116582,2-DibromopropaneHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 574231152,3-Dihydro[1,4]oxathiino[2,3-c]pyridine-7-carbaldehydeHCID 58200877(2R)-2-[(4-Amino-1-piperidinyl)methyl]-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dioneHCID 866421063,4-dihydro-2H-[1,4]oxathiepino[2,3-c]pyridine-8-carbaldehyde

Product 1

HCID 68597386(2R)-2-({4-[(3,4-Dihydro-2H-[1,4]oxathiepino[2,3-c]pyridin-8-ylmethyl)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 3,4-dihydro-2H-[1,4]oxathiepino[2,3-c]pyridine-8-carbaldehyde (29 mg, 0.895 eq.) (may be prepared analogously to the synthesis of 2,3-dihydro[1,4]oxathiino[2,3-c]pyridine-7-carbaldehyde (WO2004058144, Example 60) but replacing dibromoethane with dibromopropane) were stirred in 9:1 v:v chloroform:methanol (1 ml) for 2.5 hours. Sodium triacetoxyborohydride (105 mg, 3.000 eq.) was then added in one portion and the mixture was stirred vigorously at room temperature for 30 minutes. Saturated aqueous sodium hydrogen carbonate (0.5 ml) was then added, followed by dichloromethane (10 ml) and the mixture was stirred vigorously at room temperature for 10 min and the phases were separated (hydrophobic frit). The organic phase was evaporated under reduced pressure and the crude product was purified by column chromatography on silica (eluted with 0-12% (2M NH3 in MeOH) in DCM). Appropriate fractions were combined and evaporated under reduced pressure to give the free base of the title compound as a pale yellow solid (65 mg).

Workup

  1. stirringthe mixture was stirred vigorously at room temperature for 30 minutes
  2. stirringthe mixture was stirred vigorously at room temperature for 10 min
  3. customthe phases were separated (hydrophobic frit)
  4. customThe organic phase was evaporated under reduced pressure
  5. customthe crude product was purified by column chromatography on silica (eluted with 0-12% (2M NH3 in MeOH) in DCM)
  6. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-007ec7ceda7a4de2a6e15d444a20e033
Source dataset
uspto-grants-2013_03
Patent number
US08389524B2

Reaction notes

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