Ethanol → tert-butyl (1-(4-(2-phenethyl-9H-benzo[f]imidazo[1,2-d]pyrido[2,3-b][1,4]diazepin-3-yl)phenyl)cyclobutyl)carbamate

HRID 1046976Notes

Reaction equation

HRID 1046976 reaction equation
Br[C:2]1[N:6]2[C:7]3[CH:19]=[CH:18][CH:17]=[N:16][C:8]=3[NH:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[C:5]2=[N:4][C:3]=1[CH2:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(O)C.C(=O)(O)[O-].[Na+].CC1(C)C(C)(C)OB([C:44]2[CH:49]=[CH:48][C:47]([C:50]3([NH:54][C:55](=[O:61])[O:56][C:57]([CH3:60])([CH3:59])[CH3:58])[CH2:53][CH2:52][CH2:51]3)=[CH:46][CH:45]=2)O1>C1(C)C=CC=CC=1>[CH2:20]([C:3]1[N:4]=[C:5]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[NH:9][C:8]3[N:16]=[CH:17][CH:18]=[CH:19][C:7]=3[N:6]2[C:2]=1[C:44]1[CH:45]=[CH:46][C:47]([C:50]2([NH:54][C:55](=[O:61])[O:56][C:57]([CH3:59])([CH3:58])[CH3:60])[CH2:51][CH2:52][CH2:53]2)=[CH:48][CH:49]=1)[CH2:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 516892Sodium BicarbonateHCID 58326444tert-Butyl (1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclobutyl)carbamateHCID 1363902423-bromo-2-phenethyl-9H-benzo[f]imidazo[1,2-d]pyrido[2,3-b][1,4]diazepine

Product 1

HCID 136331867tert-butyl (1-(4-(2-phenethyl-9H-benzo[f]imidazo[1,2-d]pyrido[2,3-b][1,4]diazepin-3-yl)phenyl)cyclobutyl)carbamateYield 15.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of 3-bromo-2-phenethyl-9H-benzo[f]imidazo[1,2-d]pyrido[2,3-b][1,4]diazepine (0.197 g, 1 eq.) in a mixture of toluene (10 mL), ethanol (10 mL), and saturated sodium bicarbonate (4 mL) was added tert-butyl (1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclobutyl)carbamate (0.353 g, 2 eq.). The reaction was degassed (nitrogen) for 5 minutes and tetrakis(triphenylphosphine)palladium(0) added (0.054 g). The reaction was again degassed for 5 minutes and stirred at 100° C. overnight. The reaction mixture was cooled to room temperature and poured onto water (100 mL). The aqueous phase was extracted with dichloromethane (2×100 mL) and the organic extracts were combined and washed with brine (1×100 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by column chromatography (10-60% ethyl acetate in hexanes) gave tert-butyl (1-(4-(2-phenethyl-9H-benzo[f]imidazo[1,2-d]pyrido[2,3-b][1,4]diazepin-3-yl)phenyl)cyclobutyl)carbamate (0.042 g, 15%) as a yellow solid. LCMS: 584 [M+H].

Workup

  1. customThe reaction was degassed (nitrogen) for 5 minutes
  2. additiontetrakis(triphenylphosphine)palladium(0) added (0.054 g)
  3. customThe reaction was again degassed for 5 minutes
  4. temperatureThe reaction mixture was cooled to room temperature
  5. additionpoured onto water (100 mL)
  6. extractionThe aqueous phase was extracted with dichloromethane (2×100 mL)
  7. washwashed with brine (1×100 mL)
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customPurification by column chromatography (10-60% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-66e4935d3fab40c58fa4410a86351e51
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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