Water → (S)-1-(2-(2,6-dimethylphenyl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methylpentane-1,3-dione

HRID 80775Notes

Reaction equation

HRID 80775 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[C:9]1[N:10]=[C:11]([N:19]2[CH2:24][CH2:23][C@H:22]([O:25][CH3:26])[C:21]([CH3:28])([CH3:27])[CH2:20]2)[C:12]2[CH2:18][NH:17][CH2:16][CH2:15][C:13]=2[N:14]=1.CCC(O[C:34]([CH:36]([CH3:38])[CH3:37])=[O:35])=O.[C:39]1([CH3:45])C=CC=CC=1.[OH2:46]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[C:9]1[N:10]=[C:11]([N:19]2[CH2:24][CH2:23][C@H:22]([O:25][CH3:26])[C:21]([CH3:28])([CH3:27])[CH2:20]2)[C:12]2[CH2:18][N:17]([C:39](=[O:46])[CH2:45][C:34](=[O:35])[CH:36]([CH3:37])[CH3:38])[CH2:16][CH2:15][C:13]=2[N:14]=1

Participants

7

Reactant 4

HCID 962WaterHCID 1140TolueneHCID 22025518HCID 22025518, compoundHCID 89686034(S)-2-(2,6-dimethylphenyl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Product 1

HCID 89397283(S)-1-(2-(2,6-dimethylphenyl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methylpentane-1,3-dione

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
150 °C

Procedure

In a microwave reaction vial (S)-2-(2,6-dimethylphenyl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (115 mg, 0.302 mmol), prepared by a method similar to that described by Examples 21-c and 21-d, was combined with methyl isobutyryl acetate (65 mg, 0.45 mmol), toluene (2 mL) and DMAP (7 mg, 0.060 mmol). The vial was heated in a microwave reactor at 150° C. for 30 min. The reaction mixture was then diluted with DCM and water. The layers were separated and the aqueous phase was extracted twice with DCM. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated. The resulting residue was purified by silica gel flash column chromatography (0-100% 10:1 EtOAc:MeOH/heptanes) to provide (S)-1-(2-(2,6-dimethylphenyl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methylpentane-1,3-dione. MS (ESI+) m/z 493.0 (M+H)+

Workup

  1. customprepared by a method similar to
  2. customThe layers were separated
  3. extractionthe aqueous phase was extracted twice with DCM
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was purified by silica gel flash column chromatography (0-100% 10:1 EtOAc:MeOH/heptanes)

Sources & evidence

ORD record
ord-526c61b65e0e4ccb9806f191750e148b
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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