Morpholine → 4-(6-chloro-4-methyl-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-yl)morpholine

HRID 590828Notes

Reaction equation

HRID 590828 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([CH3:8])[C:5]2[C:9](I)=[N:10][N:11]([C:12]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:4]=2[CH:3]=1.[NH:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1.CC(C)([O-])C.[Na+].COC(C)(C)C>O1CCOCC1>[Cl:1][C:2]1[N:7]=[C:6]([CH3:8])[C:5]2[C:9]([N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)=[N:10][N:11]([C:12]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 15413tert-Butyl methyl etherHCID 23676156Sodium t-butoxideHCID 1181689626-chloro-3-iodo-4-methyl-1-trityl-1H-pyrazolo[4,3-c]pyridine2×

Product 1

HCID 1182716944-(6-chloro-4-methyl-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-yl)morpholine

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

6-Chloro-3-iodo-4-methyl-1-trityl-1H-pyrazolo[4,3-c]pyridine (Intermediate 1C; 2 g, 3.73 mmol), morpholine (0.488 mL, 5.60 mmol), sodium tert-butoxide (0.538 g, 5.60 mmol), and chloro(2-dicyclohexylphosphino-2′,6′-di-i-propoxy-1,1′-biphenyl)[2-(2-aminoethylphenyl)]palladium(II), methyl-t-butylether adduct (0.152 g, 0.187 mmol) was dissolved in dioxane (10 mL) and degassed under argon for five minutes. The reaction mixture was heated to 60° C. for 30 min under microwave irradation. The reaction mixture was diluted with ethyl acetate and washed with saturated ammonium chloride and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo while loading onto silica gel. Purification by flash chromatography (5-30% EtOAc/Hexanes) gave 4-(6-chloro-4-methyl-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-yl)morpholine. MS ESI calc'd. For C30H28ClN4O [M+H]+ 495. found 495.

Workup

  1. customdegassed under argon for five minutes
  2. additionThe reaction mixture was diluted with ethyl acetate
  3. washwashed with saturated ammonium chloride and brine
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by flash chromatography (5-30% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-feeace76552843c9a49e43d196afeae0
Source dataset
uspto-grants-2016_01
Patent number
US09233979B2

Reaction notes

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