Ethyl Bromide → Tert-butyl{1-[4-(3-ethoxy-9-phenyl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-8-yl)phenyl]cyclobutyl}carbamate

HRID 2064457Notes

Reaction equation

HRID 2064457 reaction equation
[OH:1][C:2]1[N:14]2[C:5]([C:6]3[CH:7]=[C:8]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[C:9]([C:15]4[CH:20]=[CH:19][C:18]([C:21]5([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:24][CH2:23][CH2:22]5)=[CH:17][CH:16]=4)=[N:10][C:11]=3[CH:12]=[CH:13]2)=[N:4][N:3]=1.Br[CH2:40][CH3:41]>[Ag]=O.CN1C(=O)CCC1>[CH2:40]([O:1][C:2]1[N:14]2[C:5]([C:6]3[CH:7]=[C:8]([C:33]4[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=4)[C:9]([C:15]4[CH:16]=[CH:17][C:18]([C:21]5([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:24][CH2:23][CH2:22]5)=[CH:19][CH:20]=4)=[N:10][C:11]=3[CH:12]=[CH:13]2)=[N:4][N:3]=1)[CH3:41]

Participants

5

Reactant 2

HCID 6332Ethyl BromideHCID 178452597HCID 178452597, compound

Product 1

HCID 57805453Tert-butyl{1-[4-(3-ethoxy-9-phenyl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-8-yl)phenyl]cyclobutyl}carbamate

Reagents, catalysts & solvents 2

HCID 92152Silver(II) oxideCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

To a microwave vial was added tert-butyl {1-[4-(3-hydroxy-9-phenyl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-8-yl)phenyl]cyclobutyl}carbamate (1-5e) (113 mg, 0.223 mmol), silver oxide (310 mg, 1.336 mmol), bromoethane (0.062 mL, 0.826 mmol), and finally NMP (1 mL). The reaction mixture was then heated to 80° C. under microwave irradiation for 10 minutes. Upon completion the reaction mixture was filtered and then purified by reverse phase column chromatography (Sunfire C18) eluting with 20 to 100% acetonitrile/(0.1% TFA/water) gradient. The appropriate fractions were then combined, suspended in ethyl acetate, washed with a saturated solution of sodium bicarbonate, water and brine, dried over sodium sulfate, filtered and concentrated in vacuo to give tert-butyl {1-[4-(3-ethoxy-9-phenyl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-8-yl)phenyl]cyclobutyl}carbamate (9-1) as a tan solid. MS (M+H)+: observed=536.4, calculated=536.64.

Workup

  1. filtrationUpon completion the reaction mixture was filtered
  2. custompurified by reverse phase column chromatography (Sunfire C18)
  3. washeluting with 20 to 100% acetonitrile/(0.1% TFA/water) gradient
  4. washwashed with a saturated solution of sodium bicarbonate, water and brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-51eed25c0bc646d48a103a6571492218
Source dataset
uspto-grants-2012_10
Patent number
US08288407B2

Reaction notes

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