Heptanoic acid, 7-oxo-, ethyl ester → rac-Ethyl 7-(7-methoxy-2,3-dip-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoate

HRID 406238Notes

Reaction equation

HRID 406238 reaction equation
[CH3:1][O:2][CH:3]1[CH2:26][NH:25][C:6]2=[N:7][C:8]([C:18]3[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=3)=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=3)[N:10]=[C:5]2[CH2:4]1.CCN(C(C)C)C(C)C.O=[CH:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][C:43]([O:45][CH2:46][CH3:47])=[O:44].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(Cl)Cl>[CH3:1][O:2][CH:3]1[CH2:26][N:25]([CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][C:43]([O:45][CH2:46][CH3:47])=[O:44])[C:6]2=[N:7][C:8]([C:18]3[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=3)=[C:9]([C:11]3[CH:12]=[CH:13][C:14]([CH3:17])=[CH:15][CH:16]=3)[N:10]=[C:5]2[CH2:4]1

Participants

7

Reactant 4

HCID 77609Heptanoic acid, 7-oxo-, ethyl esterHCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydride2×HCID 66665854rac-7-Methoxy-2,3-dip-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazine2×

Product 1

HCID 131731628rac-Ethyl 7-(7-methoxy-2,3-dip-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoate

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

rac-7-Methoxy-2,3-dip-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazine (Intermediate K) (80 mg, 0.232 mmol) in dry DCE (4 ml) at RT under nitrogen was treated with DIPEA (0.044 ml, 0.255 mmol) followed by ethyl 7-oxoheptanoate (80 mg, 0.463 mmol). The resulting mixture was stirred at RT for 10 minutes and treated with sodium triacetoxyborohydride (245 mg, 1.158 mmol). The mixture was heated at 60° C. for 16 hours. A further portion of sodium triacetoxyborohydride (245 mg, 1.158 mmol) was added and the mixture was heated at 50° C. for 3 days. After cooling to RT, the reaction mixture was diluted with DCM (50 ml) and washed with water (×2). The organic portion was isolated using a phase separating cartridge and the solvent was removed in vacuo. Purification of the crude product by chromatography on silica eluting with 0-20% EtOAc/iso-hexane afforded the title compound.

Workup

  1. temperatureThe mixture was heated at 60° C. for 16 hours
  2. temperaturethe mixture was heated at 50° C. for 3 days
  3. temperatureAfter cooling to RT
  4. washwashed with water (×2)
  5. customThe organic portion was isolated
  6. customseparating cartridge
  7. customthe solvent was removed in vacuo
  8. customPurification of the crude product by chromatography on silica eluting with 0-20% EtOAc/iso-hexane

Sources & evidence

ORD record
ord-e1197d1f77d9484196a81069a3dca177
Source dataset
uspto-grants-2014_06
Patent number
US08754085B2

Reaction notes

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