Sodium Sulfate → HCID 178487982, compound

HRID 657129Notes

Reaction equation

HRID 657129 reaction equation
[NH2:1][CH2:2][C@@H:3]1[CH2:8][CH2:7][CH2:6][N:5]([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)[CH2:4]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.[O-]S([O-])(=O)=O.[Na+].[Na+].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].CO.C(Cl)[Cl:61]>>[ClH:61].[ClH:61].[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:5]3[CH2:6][CH2:7][CH2:8][C@@H:3]([CH2:2][NH:1][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)[CH2:4]3)[C:12]=2[N:21]=1

Participants

6

Reactant 5

HCID 24436Sodium SulfateHCID 5049666Sodium triacetoxyborohydrideHCID 21226129Dichloromethane methanolHCID 594374057-Oxo-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine-2-carbaldehyde2×HCID 689911274-{2-[(3S)-3-(Aminomethyl)-1-piperidinyl]ethyl}-6-(methyloxy)pyrido[2,3-b]pyrazin-3(4H)-one

Product 1

HCID 178487982HCID 178487982, compound

Procedure

To a solution of 4-{2-[(3S)-3-(aminomethyl)-1-piperidinyl]ethyl}-6-(methyloxy)pyrido[2,3-b]pyrazin-3(4H)-one (0.072 g, 0.23 mmol) in 1:1 MeOH/DCM (20 mL), was added 7-oxo-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine-2-carbaldehyde (for a preparation see Example 125(c)) (0.04 g, 0.23 mmol), and excess Na2SO4. The solution was stirred at ambient temperature for 16 h followed by the addition of NaBH(OAc)3 (1.68 g, 7.92 mmol). The resulting solution was stirred for an additional 2 hours. Analysis by LCMS showed only 50% product, therefore an additional portion of 7-oxo-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine-2-carbaldehyde (0.04 g, 0.23 mmol) was added and the reaction was stirred for an additional 16 h. The solution was 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 to yield the free base of the desired product as a yellow oily film (0.034 g, 32%). LCMS: m/z 479.2 (MH+). 1H NMR (400 MHz, CDCl3) δ 1.57-1.69 (m, 2H) 1.73-1.82 (m, 1H) 1.95 (d, J=8.59 Hz, 21H) 2.18 (td, J=10.99, 3.03 Hz, 1H) 2.51-2.63 (m, 21H) 2.67-2.75 (m, 4H) 2.81-2.92 (m, 1H) 2.92-3.01 (m, 2H) 3.21-3.32 (m, 1H) 3.88-4.00 (m, 2H) 4.00-4.05 (m, 3H) 4.57-4.68 (m, 2H) 6.73 (d, J=8.59 Hz, 1H) 8.00-8.04 (m, 1H) 8.23 (s, 1H) 8.36 (s, 1H).

Workup

  1. stirringThe resulting solution was stirred for an additional 2 hours
  2. stirringthe reaction was stirred for an additional 16 h
  3. concentrationThe solution was then concentrated onto silica gel under vacuum
  4. customthe crude residue purified by column chromatography (silica gel)

Sources & evidence

ORD record
ord-9352693a628e4a71b8bee9912095b3a8
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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