tert-Butanol → HCID 67386358, compound

HRID 1898612Notes

Reaction equation

HRID 1898612 reaction equation
[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9](=[O:36])[C@H:10]([NH:14][C:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([C:26]#[CH:27])[N:24]=3)[N:19]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33])[CH:18]=2)=[O:16])[CH:11]2[CH2:13][CH2:12]2)[CH2:5][CH2:4]1)#[N:2].[N:37]([CH:40]1[CH2:44][CH2:43][CH2:42][CH2:41]1)=[N+:38]=[N-:39].CC(O)(C)C>S([O-])([O-])(=O)=O.[Cu+2].[Cu].O>[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9](=[O:36])[C@H:10]([NH:14][C:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([C:26]4[N:39]=[N:38][N:37]([CH:40]5[CH2:44][CH2:43][CH2:42][CH2:41]5)[CH:27]=4)[N:24]=3)[N:19]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:34])([CH3:33])[CH3:35])[CH:18]=2)=[O:16])[CH:11]2[CH2:12][CH2:13]2)[CH2:5][CH2:4]1)#[N:2]

Participants

7

Reactant 3

HCID 6386tert-ButanolHCID 141819AzidocyclopentaneHCID 58438633HCID 58438633, compound

Product 1

HCID 67386358HCID 67386358, compoundYield 70%

Reagents, catalysts & solvents 3

HCID 23978CopperCatalystHCID 24462Copper SulfateCatalystHCID 962WaterSolvent

Conditions

Temperature
125 °C

Procedure

A microwave vial was charged with 2-ethynyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide (100 mg, 0.20 mmol), azidocyclopentane (32.9 mg, 0.3 mmol), t-BuOH (0.6 mL), and H2O (0.6 mL). To this sticky mixture was added 1.0 M aqueous copper (II) sulfate (39.5 μL, 0.04 mmol) and copper powder (10.0 mg, 0.16 mmol). The vial was sealed and the heterogeneous reaction mixture was heated in a microwave reactor at 125° C. for 5 min. The reaction mixture was cooled to room temperature and filtered, rinsing with EtOAc. The filtrate was washed with water, dried over MgSO4, and concentrated. The residue was purified by silica gel chromatography (50% to 100% EtOAc/hexanes) to afford 85 mg (70%) of 2-(1-cyclopentyl-1H-[1,2,3]triazol-4-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide as an off-white foamy solid.

Workup

  1. customThe vial was sealed
  2. temperatureThe reaction mixture was cooled to room temperature
  3. filtrationfiltered
  4. washrinsing with EtOAc
  5. washThe filtrate was washed with water
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography (50% to 100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-1c72b02119b64e21aa7b0a04f0915bf5
Source dataset
uspto-grants-2013_08
Patent number
US08518945B2

Reaction notes

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