Acetic Acid → (2S,4S)-tert-butyl 4-(4-amino-5-((3,5-dimethoxyphenyl)ethynyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-(1,3,4-oxadiazole-2-yl)pyrrolidine-1-carboxylate

HRID 516180Notes

Reaction equation

HRID 516180 reaction equation
[C:1]1(C)C=CC=CC=1.C(OC)(OC)OC.[NH2:15][C:16]1[C:17]2[C:24]([C:25]#[C:26][C:27]3[CH:32]=[C:31]([O:33][CH3:34])[CH:30]=[C:29]([O:35][CH3:36])[CH:28]=3)=[CH:23][N:22]([C@@H:37]3[CH2:41][N:40]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[C@H:39]([C:49]([NH:51][NH2:52])=[O:50])[CH2:38]3)[C:18]=2[N:19]=[CH:20][N:21]=1.C(O)(=O)C>O.C(OCC)(=O)C>[NH2:15][C:16]1[C:17]2[C:24]([C:25]#[C:26][C:27]3[CH:32]=[C:31]([O:33][CH3:34])[CH:30]=[C:29]([O:35][CH3:36])[CH:28]=3)=[CH:23][N:22]([C@@H:37]3[CH2:41][N:40]([C:42]([O:44][C:45]([CH3:46])([CH3:47])[CH3:48])=[O:43])[C@H:39]([C:49]4[O:50][CH:1]=[N:52][N:51]=4)[CH2:38]3)[C:18]=2[N:19]=[CH:20][N:21]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 1140TolueneHCID 9005Trimethyl orthoformateHCID 89870936(2S,4S)-tert-butyl 4-(4-amino-5-((3,5-dimethoxyphenyl)ethynyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-(hydrazine carbonyl)pyrrolidine-1-carboxylate

Product 1

HCID 89870878(2S,4S)-tert-butyl 4-(4-amino-5-((3,5-dimethoxyphenyl)ethynyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-(1,3,4-oxadiazole-2-yl)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

Toluene (3 ml) and trimethyl orthoformate (79 μl) were added to the (2S,4S)-tert-butyl 4-(4-amino-5-((3,5-dimethoxyphenyl)ethynyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-(hydrazine carbonyl)pyrrolidine-1-carboxylate (93.6 mg) obtained in Step 2, and the resulting mixture was stirred at 110° C. overnight. Acetic acid (400 μl) was added to the reaction mixture, and stirred at 110° C. for 6 hours. Ethyl acetate and water were added to the reaction mixture to separate the organic layer. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The resulting residue was purified by silica gel column chromatography (developing solvent: chloroform/methanol) to obtain the title compound as a light-yellow, amorphous substance (50 mg). Physical properties: m/z [M+H]+ 532.2

Workup

  1. stirringstirred at 110° C. for 6 hours
  2. customto separate the organic layer
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. distillationthe solvent was distilled off under reduced pressure
  5. customThe resulting residue was purified by silica gel column chromatography (developing solvent: chloroform/methanol)

Sources & evidence

ORD record
ord-97a440ef8b064776ae51d066ec7cd9f3
Source dataset
uspto-grants-2015_08
Patent number
US09108973B2

Reaction notes

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