8-Hydroxyquinoline → HCID 67386074, compound

HRID 1898651Notes

Reaction equation

HRID 1898651 reaction equation
[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]([C@H:11]([NH:16][C:17]([C:19]2[C:27]3[C:22](=[N:23][CH:24]=[C:25](Br)[N:26]=3)[N:21]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[CH:20]=2)=[O:18])[C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1)#[N:2].[OH:37][C:38]1[CH:39]=[CH:40][CH:41]=[C:42]2[C:47]=1N=CC=C2.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(O)CCCCC1>CCOC(C)=O.[Cu]I>[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]([C@H:11]([NH:16][C:17]([C:19]2[C:27]3[C:22](=[N:23][CH:24]=[C:25]([O:37][CH:38]4[CH2:39][CH2:40][CH2:41][CH2:42][CH2:47]4)[N:26]=3)[N:21]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[CH:20]=2)=[O:18])[C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1)#[N:2]

Participants

7

Reactant 4

HCID 19238-HydroxyquinolineHCID 7966CyclohexanolHCID 62657Potassium Phosphate, TribasicHCID 584385322-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-]pyrazine-7-carboxylic acid [(R)-1-(4-cyano-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amide

Product 1

HCID 67386074HCID 67386074, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A 10 mL flask was charged with 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyano-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amide (100 mg, 0.17 mmol, copper(I) iodide (1.7 mg, 0.009 mmol), 8-hydroxyquinoline (2.5 mg, 0.017 mmol) and potassium phosphate tribasic (74 mg, 0.34 mmol) under argon atmosphere. Cyclohexanol (1.82 mL, 17.3 mmol) was added and the reaction mixture was heated at 120° C. for 24 h. The reaction mixture was allowed to reach room temperature and then diluted with EtOAc (10 mL). The slurry was filtered over a celite pad and the filtrate was evaporated under vacuum. The crude residue was purified by preparative TLC (SiO2, Hex:EtOAc, 1:1×2) to give 52 mg (50%) of 2-cyclohexyloxy-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyano-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amide. (M+Na)+=619.

Workup

  1. customto reach room temperature
  2. filtrationThe slurry was filtered over a celite pad
  3. customthe filtrate was evaporated under vacuum
  4. customThe crude residue was purified by preparative TLC (SiO2, Hex:EtOAc, 1:1×2)

Sources & evidence

ORD record
ord-59c0c9bddfd146f38bd8004b12ec5ecf
Source dataset
uspto-grants-2013_08
Patent number
US08518945B2

Reaction notes

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