Ethanol → HCID 69087617, compound

HRID 1046966Notes

Reaction equation

HRID 1046966 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:48]3([NH:52][C:53](=[O:59])[O:54][C:55]([CH3:58])([CH3:57])[CH3:56])[CH2:51][CH2:50][CH2:49]3)=[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:48]3([NH:52][C:53](=[O:59])[O:54][C:55]([CH3:58])([CH3:56])[CH3:57])[CH2:51][CH2:50][CH2:49]3)=[CH:46][CH:47]=2)[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=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 675030133-bromo-2-phenyl-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepine

Product 1

HCID 69087617HCID 69087617, compoundYield 52.5%

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 (0.800 g, 1 eq.) in a mixture of toluene (10 mL), ethanol (10 mL), and saturated sodium bicarbonate (2 mL) was added tert-butyl (1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclobutyl)carbamate (1.15 g, 1.5 eq.). The reaction was degassed (nitrogen) for 5 minutes and tetrakis(triphenylphosphine)palladium(0) added (0.08 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 (2×75 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 (1-(4-(2-phenyl-9H-benzo[f]imidazo[1,2-d]pyrido[2,3-b][1,4]diazepin-3-yl)phenyl)cyclobutyl)carbamate (0.6 g, 52%). 1H NMR (DMSO-d6) 400 MHz δ 8.41 (s, 1H), 8.04 (dd, JA=4.8 Hz, JB=1.6 Hz, 1H), 7.96 (dd, JA=7.6 Hz, JB=1.6 Hz, 1H), 7.53-7.48 (m, 2H), 7.45-7.08 (m, 11H), 6.91-6.86 (m, 1H), 6.67-6.62 (m, 1H), 2.45-2.32 (m, 4H), 2.07-1.94 (m, 1H), 1.85-1.73 (m, 1H), 1.28 (bs, 9H); LCMS: 556 [M+H].

Workup

  1. customThe reaction was degassed (nitrogen) for 5 minutes
  2. additiontetrakis(triphenylphosphine)palladium(0) added (0.08 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 (2×75 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-1fb52483b61d454e85055462390d9357
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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