Carbonic acid-guanidine (1:1) → 6-{2-[(4-Methoxybenzyl)oxy]-4-methylpyridin-3-yl}-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine

HRID 632832Notes

Reaction equation

HRID 632832 reaction equation
CN([CH:4]=[C:5]1[C:10](=O)[CH2:9][CH2:8][N:7]([C:12]2[C:13]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=3)=[N:14][CH:15]=[CH:16][C:17]=2[CH3:18])[CH2:6]1)C.C(=O)(O)O.[NH2:33][C:34]([NH2:36])=[NH:35].O.O.O.C([O-])(=O)C.[Na+]>CO>[CH3:28][O:27][C:24]1[CH:25]=[CH:26][C:21]([CH2:20][O:19][C:13]2[C:12]([N:7]3[CH2:8][CH2:9][C:10]4[N:35]=[C:34]([NH2:36])[N:33]=[CH:4][C:5]=4[CH2:6]3)=[C:17]([CH3:18])[CH:16]=[CH:15][N:14]=2)=[CH:22][CH:23]=1

Participants

5

Reactant 3

HCID 286947Carbonic acid-guanidine (1:1)HCID 23665404Sodium Acetate TrihydrateHCID 1212495693-Dimethylaminomethylene-2'-(4-methoxybenzyloxy)-4'-methyl-2,3,5,6-tetrahydro[1,3']bipyridinyl-4-one

Product 1

HCID 1212495386-{2-[(4-Methoxybenzyl)oxy]-4-methylpyridin-3-yl}-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amineYield 37%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 3-dimethylaminomethylene-2′-(4-methoxybenzyloxy)-4′-methyl-2,3,5,6-tetrahydro[1,3′]bipyridinyl-4-one (5.21 g, 13.66 mmol) in methanol (340 ml) was treated with guanidine carbonate (9.84 g, 54.63 mmol), followed by addition of sodium acetate trihydrate (14.87 g, 109.28 mmol) and the reaction mixture was refluxed for 3 hours. The solvent was removed in vacuo and the residue was partitioned between water and dichloromethane. The separated organic layer was dried (MgSO4), filtered, and concentrated to a red oil. The oil was taken up in a minimal volume of EtOAc and allowed to stand overnight at room temperature. The resulting yellow, crystalline solid was collected, washed with EtOAc, and dried to give the title compound (1.91 g). The mother liquor was concentrated and the residue was eluted through a flash column (silica gel 60, 230-400 mesh, EtOAc) to obtain an additional lot of the title compound (1.05 g) The total amount 2.96 g, 57%). HPLC analysis showed the compound has a purity of 98%.

Workup

  1. temperaturethe reaction mixture was refluxed for 3 hours
  2. customThe solvent was removed in vacuo
  3. customthe residue was partitioned between water and dichloromethane
  4. dry with materialThe separated organic layer was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated to a red oil
  7. customThe resulting yellow, crystalline solid was collected
  8. washwashed with EtOAc
  9. customdried

Sources & evidence

ORD record
ord-5ccbf32656194d1f8b17be03df491a2d
Source dataset
uspto-grants-2016_04
Patent number
US09321766B1

Reaction notes

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