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

HRID 1046962Notes

Reaction equation

HRID 1046962 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[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(O)C.C(=O)(O)[O-].[Na+].[C:34]([O:38][C:39]([NH:41][CH2:42][C:43]1[CH:48]=[CH:47][C:46](B(O)O)=[CH:45][CH:44]=1)=[O:40])([CH3:37])([CH3:36])[CH3:35]>C1(C)C=CC=CC=1>[C:20]1([C:3]2[N:4]=[C:5]3[C:11]4[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=4[NH:9][C:8]4[N:16]=[CH:17][CH:18]=[CH:19][C:7]=4[N:6]3[C:2]=2[C:46]2[CH:47]=[CH:48][C:43]([CH2:42][NH:41][C:39](=[O:40])[O:38][C:34]([CH3:37])([CH3:36])[CH3:35])=[CH:44][CH:45]=2)[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 516892Sodium BicarbonateHCID 38631634-(tert-Butoxycarbonylaminomethyl)phenylboronic acidHCID 675030133-bromo-2-phenyl-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepine

Product 1

HCID 67503559tert-butyl 4-(2-phenyl-9H-benzo[f]imidazo[1,2-d]pyrido[2,3-b][1,4]diazepin-3-yl)benzylcarbamateYield 64.8%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of 3-bromo-2-phenyl-9H-benzo[f]imidazo[1,2-d]pyrido[2,3-b][1,4]diazepine (0.250 g, 1 eq.) in a mixture of toluene (5 mL), ethanol (5 mL), and saturated sodium bicarbonate (1 mL) was added (4-(((tert-butoxycarbonyl)amino)methyl)phenyl)boronic acid (0.1 g, 1.5 eq.). The reaction was degassed (nitrogen) for 5 minutes and tetrakis(triphenylphosphine)palladium(0) added (0.025 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 (50 mL). The aqueous phase was extracted with dichloromethane (2×50 mL) and the organic extracts were combined and washed with water (1×50 mL), brine (1×50 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by column chromatography (25-75% ethyl acetate in hexanes) gave the product which was triturated with ether to give tert-butyl 4-(2-phenyl-9H-benzo[f]imidazo[1,2-d]pyrido[2,3-b][1,4]diazepin-3-yl)benzylcarbamate (0.133 g, 40%). LCMS: 516 [M+H].

Workup

  1. customThe reaction was degassed (nitrogen) for 5 minutes
  2. additiontetrakis(triphenylphosphine)palladium(0) added (0.025 g)
  3. customThe reaction was again degassed for 5 minutes
  4. temperatureThe reaction mixture was cooled to room temperature
  5. additionpoured onto water (50 mL)
  6. extractionThe aqueous phase was extracted with dichloromethane (2×50 mL)
  7. washwashed with water (1×50 mL), brine (1×50 mL)
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customPurification by column chromatography (25-75% ethyl acetate in hexanes)
  12. customgave the product which
  13. customwas triturated with ether

Sources & evidence

ORD record
ord-c5a55439cc2f433582c08e2a188411f2
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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