(R)-ethyl 4-chloro-2-(tetrahydro-2H-pyran-4-ylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidine-7-carboxylate → (R)-ethyl 2-(tetrahydro-2H-pyran-4-ylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidine-7-carboxylate

HRID 2279597Notes

Reaction equation

HRID 2279597 reaction equation
Cl[C:2]1[C:3]2[CH2:18][CH2:17][C@H:16]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[O:15][C:4]=2[N:5]=[C:6]([NH:8][CH:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[N:7]=1>[Pd].CCOC(C)=O>[O:12]1[CH2:13][CH2:14][CH:9]([NH:8][C:6]2[N:7]=[CH:2][C:3]3[CH2:18][CH2:17][C@H:16]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[O:15][C:4]=3[N:5]=2)[CH2:10][CH2:11]1

Participants

4

Reactant 1

HCID 86705580(R)-ethyl 4-chloro-2-(tetrahydro-2H-pyran-4-ylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidine-7-carboxylate

Product 1

HCID 86705579(R)-ethyl 2-(tetrahydro-2H-pyran-4-ylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidine-7-carboxylateYield 84.6%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 404 (0.525 g, 1.23 mmol) and EtOAc (15 mL) was subjected to vacuum/nitrogen purge cycles then Pd/C (0.392 g, 0.369 mmol, 10% Degussa) was added and the solution stirred for 2 h under H2 (H2 balloon). The mixture was filtered and the solid washed with EtOAc and the filterate passed through a 0.45 micron frit and then concentrated. The crude product was purified by SiO2 chromatography eluting with MeOH/DCM (5:95) to afford 0.32 g (77%) of (R)-ethyl 2-(tetrahydro-2H-pyran-4-ylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidine-7-carboxylate (406) as a clear oil: MS m/z (APCI-pos) M+1=308.1.

Workup

  1. custompurge cycles
  2. filtrationThe mixture was filtered
  3. washthe solid washed with EtOAc
  4. concentrationconcentrated
  5. customThe crude product was purified by SiO2 chromatography
  6. washeluting with MeOH/DCM (5:95)

Sources & evidence

ORD record
ord-16338832e01d432b8fa9d961b38267ca
Source dataset
uspto-grants-2015_09
Patent number
US09133187B2

Reaction notes

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