Ethanol → HCID 69087680, compound

HRID 1046964Notes

Reaction equation

HRID 1046964 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+].CC1(C)C(C)(C)OB([C:42]2[CH:47]=[CH:46][C:45]([C@@H:48]([NH:50][C:51](=[O:57])[O:52][C:53]([CH3:56])([CH3:55])[CH3:54])[CH3:49])=[CH:44][CH:43]=2)O1>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:42]2[CH:43]=[CH:44][C:45]([C@@H:48]([NH:50][C:51](=[O:57])[O:52][C:53]([CH3:56])([CH3:55])[CH3:54])[CH3:49])=[CH:46][CH:47]=2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 516892Sodium BicarbonateHCID 67451913(S)-tert-butyl (1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)carbamateHCID 675030133-bromo-2-phenyl-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepine

Product 1

HCID 69087680HCID 69087680, compoundYield 31%

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 (0.60 g, 1 eq.) in a mixture of toluene (10 mL), ethanol (10 mL), and saturated sodium bicarbonate (3 mL) was added (S)-tert-butyl (1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)carbamate (1.31 g, 2.45 eq.). The reaction was degassed (nitrogen) for 5 minutes and tetrakis(triphenylphosphine)palladium(0) added (0.3 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 (S)-tert-butyl (1-(4-(2-phenyl-9H-benzo[f]imidazo[1,2-d]pyrido[2,3-b][1,4]diazepin-3-yl)phenyl)ethyl)carbamate (0.251 g, 31%). LCMS: 530 [M+H].

Workup

  1. customThe reaction was degassed (nitrogen) for 5 minutes
  2. additiontetrakis(triphenylphosphine)palladium(0) added (0.3 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-6d5eadb9cda9428690a1366c0b5a01d0
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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