Isopropanol → HCID 66927717, compound

HRID 1175727Notes

Reaction equation

HRID 1175727 reaction equation
C(O)(C)C.C([O-])=O.[NH4+].Cl[C:10]1[N:11]=[C:12]([N:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)[C:13]2[N:19]=[C:18]([C:20]([O:22][CH3:23])=[O:21])[CH:17]=[C:16](Cl)[C:14]=2[N:15]=1>O.[Pd]>[N:25]1([C:12]2[C:13]3[N:19]=[C:18]([C:20]([O:22][CH3:23])=[O:21])[CH:17]=[CH:16][C:14]=3[N:15]=[CH:10][N:11]=2)[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1

Participants

6

Reactant 3

HCID 3776IsopropanolHCID 2723923Ammonium formate3×HCID 86624201HCID 86624201, compound2×

Product 1

HCID 66927717HCID 66927717, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 962WaterSolvent4×

Procedure

To a round-bottom flask were added palladium (540 mg; 0.51 mmol; 0.05 eq.) isopropanol (90 mL). Ar was bubbled in this mixture. A degassed ammonium formate solution in water (2.56 g, 40.6 mmol, 4 eq., in 4 mL of water) was added, followed by methyl 2,8-dichloro-4-(1-piperidinyl)pyrido[3,2-d]pyrimidine-6-carboxylate (Intermediate 1.4) (3.46 g; 10.5 mmol; 1 eq.) and degassed isopropanol (10 mL). After 30 min, a second batch of ammonium formate was added as solution in water (2.56 g, 40.6 mmol, 4 eq., in 4 mL of water). Finally, after additional 30 min, another 8 equivalents of ammonium formate in water were (5.12 g, 81.2 mmol, 8 eq., in 8 mL of water). The mixture was then stirred at rt. overnight and filtered through celite. The filtrate was evaporated. The crude product was dissolved in DCM and washed with water and brine. Organic phase was dried over magnesium sulfate, filtered and evaporated to give methyl 4-(1-piperidinyl)pyrido[3,2-d]pyrimidine-6-carboxylate (2.29 g; 83%) (Intermediate 1.5), as a yellow solid in 92.9% HPLC purity. This product was used in the next step without further purification.

Workup

  1. customAr was bubbled in this mixture
  2. customdegassed isopropanol (10 mL)
  3. waitFinally, after additional 30 min
  4. filtrationovernight and filtered through celite
  5. customThe filtrate was evaporated
  6. dissolutionThe crude product was dissolved in DCM
  7. washwashed with water and brine
  8. dry with materialOrganic phase was dried over magnesium sulfate
  9. filtrationfiltered
  10. customevaporated

Sources & evidence

ORD record
ord-d1cc80b299534c6a97ef00ccd1e8e120
Source dataset
uspto-grants-2010_11
Patent number
US07842698B2

Reaction notes

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