Isopropanol → HCID 66927717, compound

HRID 556424Notes

Reaction equation

HRID 556424 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 3776Isopropanol2×HCID 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 degazed 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 degazed 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. waitFinally, after additional 30 min
  3. filtrationovernight and filtered through celite
  4. customThe filtrate was evaporated
  5. dissolutionThe crude product was dissolved in DCM
  6. washwashed with water and brine
  7. dry with materialOrganic phase was dried over magnesium sulfate
  8. filtrationfiltered
  9. customevaporated

Sources & evidence

ORD record
ord-503dbc293afb4ff493fade84ce6b97e6
Source dataset
uspto-grants-2011_11
Patent number
US08058289B2

Reaction notes

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