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 2104136Notes

Reaction equation

HRID 2104136 reaction equation
[C:1]([O:5][C:6](=[O:38])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:27]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[CH:26][C:25]4[C:24]5=[N:34][N:35]=[C:36]([OH:37])[N:23]5[CH:22]=[CH:21][C:20]=4[N:19]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].Br[CH2:40][CH3:41]>[Ag]=O.CN1C(=O)CCC1>[C:1]([O:5][C:6](=[O:38])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:27]([C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)=[CH:26][C:25]4[C:24]5=[N:34][N:35]=[C:36]([O:37][CH2:40][CH3:41])[N:23]5[CH:22]=[CH:21][C:20]=4[N:19]=3)=[CH:14][CH:13]=2)[CH2:9][CH2:10][CH2:11]1)([CH3:4])([CH3:2])[CH3:3]

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-7c2d1d76414340818ec94ec4a405467d
Source dataset
uspto-grants-2009_08
Patent number
US07576209B2

Reaction notes

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