Methyl 4-methyl-3-oxopentanoate → 1-(4-methoxy-2-(3-methyl-1-tosyl-1H-indol-4-yl)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methylpentane-1,3-dione

HRID 80802Notes

Reaction equation

HRID 80802 reaction equation
[CH3:1][O:2][C:3]1[C:4]2[CH2:32][NH:31][CH2:30][CH2:29][C:5]=2[N:6]=[C:7]([C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[C:11]([CH3:28])=[CH:12][N:13]3[S:18]([C:21]2[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=2)(=[O:20])=[O:19])[N:8]=1.[CH3:33][CH:34]([CH3:42])[C:35](=[O:41])[CH2:36][C:37](OC)=[O:38]>C1(C)C=CC=CC=1.CN(C1C=CN=CC=1)C.ClCCl.O>[CH3:1][O:2][C:3]1[C:4]2[CH2:32][N:31]([C:37](=[O:38])[CH2:36][C:35](=[O:41])[CH:34]([CH3:42])[CH3:33])[CH2:30][CH2:29][C:5]=2[N:6]=[C:7]([C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[C:11]([CH3:28])=[CH:12][N:13]3[S:18]([C:21]2[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=2)(=[O:20])=[O:19])[N:8]=1

Participants

7

Reactant 2

HCID 2759969Methyl 4-methyl-3-oxopentanoateHCID 712404804-methoxy-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Product 1

HCID 866902601-(4-methoxy-2-(3-methyl-1-tosyl-1H-indol-4-yl)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methylpentane-1,3-dione

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 4-methoxy-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine, prepared as described in Example 17, (300 mg, 0.67 mmol) in toluene (3 mL), in a 2-5 mL microwave vial, was added methyl 4-methyl-3-oxopentanoate (0.28 mL, 2 mmol) followed by DMAP (25 mg, 0.2 mmol). The reaction vessel was then sealed and heated via microwave irradiation at 150° C. for 35 min. The reaction mixture was then cooled to room temperature and diluted with dichloromethane and water. The layers were separated and the organic layer was dried by passing through a phase separator and then concentrated. The resulting residue was purified via silica gel flash chromatography (45-90% ethyl acetate/heptanes) to furnish 1-(4-methoxy-2-(3-methyl-1-tosyl-1H-indol-4-yl)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methylpentane-1,3-dione. MS (ESI+) m/z 561.3 (M+H)+.

Workup

  1. customThe reaction vessel was then sealed
  2. temperatureThe reaction mixture was then cooled to room temperature
  3. customThe layers were separated
  4. customthe organic layer was dried
  5. concentrationconcentrated
  6. customThe resulting residue was purified via silica gel flash chromatography (45-90% ethyl acetate/heptanes)

Sources & evidence

ORD record
ord-c446987a847e49b88828cdc6965fed80
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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