Cesium fluoride → HCID 53386257, compound

HRID 1898532Notes

Reaction equation

HRID 1898532 reaction equation
[OH:1][C:2]1([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH2:7][CH2:6][N:5]([C:8]([C@H:10]([NH:15][C:16]([C:18]2[C:26]3[C:21](=[N:22][CH:23]=[C:24]([CH:27]4[CH2:29][CH2:28]4)[N:25]=3)[N:20](COCC[Si](C)(C)C)[CH:19]=2)=[O:17])[C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.C1OCCOCCOCCOCCOCCOC1.[F-].[Cs+]>C(#N)C>[OH:1][C:2]1([C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH2:3][CH2:4][N:5]([C:8]([C@H:10]([NH:15][C:16]([C:18]2[C:26]3[C:21](=[N:22][CH:23]=[C:24]([CH:27]4[CH2:28][CH2:29]4)[N:25]=3)[NH:20][CH:19]=2)=[O:17])[C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]1

Participants

5

Reactant 3

HCID 25953Cesium fluorideHCID 2855718-Crown-6HCID 67386679HCID 67386679, compound

Product 1

HCID 53386257HCID 53386257, compoundYield 28.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
85 °C

Procedure

In a round-bottomed flask, 2-cyclopropyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-hydroxy-4-phenyl-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amide (0.21 g, 0.33 mmol) was dissolved in acetonitrile (4.2 mL). 18-Crown-6 (89 mg, 0.33 mmol) and cesium fluoride (507 mg, 3.34 mmol) were added. The reaction mixture was stirred at 85° C. overnight and then at room temperature for 24 h. Silica Gel (˜1 g) was added to the reaction mixture and the suspension was concentrated and purified by chromatography over 12 g SiO2 with 0-100% EtOAc/heptane to 0-10% MeOH/EtOAc to afford an oil. Trituration with dichloromethane/hexanes afforded 45 mg (26%) of 2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-hydroxy-4-phenyl-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amide as a yellow powder. MS: (M+H)+=476.

Workup

  1. waitat room temperature for 24 h
  2. additionSilica Gel (˜1 g) was added to the reaction mixture
  3. concentrationthe suspension was concentrated
  4. custompurified by chromatography over 12 g SiO2 with 0-100% EtOAc/heptane to 0-10% MeOH/EtOAc
  5. customto afford an oil

Sources & evidence

ORD record
ord-c47d26b40b7e43cba870d936d80a594d
Source dataset
uspto-grants-2013_08
Patent number
US08518945B2

Reaction notes

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