Sodium Sulfate → HCID 178487984, compound

HRID 657099Notes

Reaction equation

HRID 657099 reaction equation
[ClH:1].[NH2:2][CH:3]1[CH2:8][CH2:7][N:6]([CH2:9][CH2:10][N:11]2[C:16](=[O:17])[CH:15]=[N:14][C:13]3[CH:18]=[CH:19][C:20]([O:22][CH3:23])=[N:21][C:12]2=3)[CH2:5][CH2:4]1.[O:24]=[C:25]1[NH:36][C:29]2[N:30]=[C:31]([CH:34]=O)[N:32]=[CH:33][C:28]=2[CH2:27][CH2:26]1.C([O-])(O)=O.[Na+].[O-]S([O-])(=O)=O.[Na+].[Na+].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].CO.[CH2:65]([Cl:67])[Cl:66]>>[CH2:65]([Cl:67])[Cl:66].[CH2:65]([Cl:67])[Cl:66].[CH3:16][OH:17].[NH4+:2].[OH-:24].[ClH:1].[CH3:23][O:22][C:20]1[CH:19]=[CH:18][C:13]2[N:14]=[CH:15][C:16](=[O:17])[N:11]([CH2:10][CH2:9][N:6]3[CH2:5][CH2:4][CH:3]([NH:2][CH2:34][C:31]4[NH:30][C:29]5=[N:36][C:25](=[O:24])[CH2:26][CH2:27][C:28]5=[CH:33][N:32]=4)[CH2:8][CH2:7]3)[C:12]=2[N:21]=1

Participants

8

Reactant 6

HCID 24436Sodium SulfateHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 21226129Dichloromethane methanolHCID 594374057-Oxo-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine-2-carbaldehydeHCID 689298784-(2-(4-aminopiperidin-1-yl)ethyl)-6-methoxypyrido(2,3-b)pyrazin-3(4H)-one hydrochloride

Product 2

HCID 86635354DCM DCM MeOH NH4OHHCID 178487984HCID 178487984, compoundYield 43%

Procedure

To a solution of 4-[2-(4-amino-1-piperidinyl)ethyl]-6-(methyloxy)pyrido[2,3-b]pyrazin-3(4H)-one hydrochloride (see Example 126(m) for a preparation) (0.600 g, 1.98 mmol) in 1:1 MeOH/DCM, was added 7-oxo-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine-2-carbaldehyde (0.350 g, 1.98 mmol), NaHCO3 (0.831 g, 9.90 mmol), and excess Na2SO4. The solution was stirred at ambient temperature overnight, followed by the addition of NaBH(OAc)3 (1.68 g, 7.92 mmol). The resulting solution was stirred for an additional 1 h, then concentrated onto silica gel under vacuum and the crude residue purified by column chromatography (silica gel) using a DCM/DCM-MeOH—NH4OH (90:10:1) gradient, followed by a further purification using 10% MeOH/DCM and then DCM/DCM-MeOH—NH4OH (90:1:0.1) to yield the free base of the desired product (0.396 g, 43%). LCMS: m/z 465.2 (MH+). 1H NMR (400 MHz, CDCl3) δ 1.42-1.53 (m, 2H) 1.90 (d, J=10.86 Hz, 2H) 2.18 (t, J=10.61 Hz, 2H) 2.52-2.60 (m, 1H) 2.66-2.77 (m, 5H) 2.93 (t, J=7.71 Hz, 2H) 3.07 (d, J=11.62 Hz, 2H) 3.98 (s, 2H) 4.00-4.03 (m, 3H) 4.52-4.62 (m, 2H) 6.70 (d, J=8.84 Hz, 1H) 7.99 (d, J=8.59 Hz, 1H) 8.12 (s, 1H) 8.34 (s, 1H).

Workup

  1. stirringThe resulting solution was stirred for an additional 1 h
  2. concentrationconcentrated onto silica gel under vacuum
  3. customthe crude residue purified by column chromatography (silica gel)
  4. customfollowed by a further purification

Sources & evidence

ORD record
ord-2e20f2547226408481964f8a09e868ed
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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