Ethanol → HCID 69087651, compound

HRID 1046988Notes

Reaction equation

HRID 1046988 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][C:23]([C:26]2([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:29][CH2:28][CH2:27]2)=[CH:22][CH:21]=1.C(O)C.C(=O)(O)[O-].[Na+].[C:46]1(B(O)O)[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1>C1(C)C=CC=CC=1>[C:46]1([C:2]2[N:6]3[C:7]4[CH:19]=[CH:18][CH:17]=[N:16][C:8]=4[NH:9][C:10]4[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=4[C:5]3=[N:4][C:3]=2[C:20]2[CH:21]=[CH:22][C:23]([C:26]3([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:34])([CH3:35])[CH3:36])[CH2:29][CH2:28][CH2:27]3)=[CH:24][CH:25]=2)[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 66827Phenylboronic AcidHCID 516892Sodium BicarbonateHCID 69087643HCID 69087643, compound

Product 1

HCID 69087651HCID 69087651, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of tert-butyl (1-(4-(3-bromo-9H-benzo[f]imidazo[1,2-d]pyrido[2,3-b][1,4]diazepin-2-yl)phenyl)cyclobutyl)carbamate (0.213 g, 1 eq.) in a mixture of toluene (5 mL), ethanol (5 mL), and saturated sodium bicarbonate (1 mL) was added phenyl boronic acid (0.07 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 (1-(4-(3-phenyl-9H-benzo[f]imidazo[1,2-d]pyrido[2,3-b][1,4]diazepin-2-yl)phenyl)cyclobutyl)carbamate (0.084 g, 40%) as a yellow solid. 1H NMR (DMSO-d6) 400 MHz δ 8.55 (s, 1 H), 8.06 (dd, JA=4.8 Hz, JB=2.4 Hz, 1H), 7.95 (dd, JA=7.6 Hz, JB=1.2 Hz, 1H), 7.78 (dd, JA=7.6 Hz, JB=1.6 Hz, 1H), 7.58-7.50 (m, 1H), 7.44-7.36 (m, 4H), 7.35-7.31 (m, 2H), 7.30-7.18 (m, 4H), 7.14-7.09 (m, 1H), 6.89 (dd, JA=7.6 Hz, JB=1.2 Hz, 1H), 6.73 (dd, JA=7.6 Hz, JB=4.8 Hz, 1H), 2.45-2.28 (m, 4H), 2.04-1.92 (m, 1H), 1.83-1.70 (m, 1H), 1.33 (br. s, 9H); LCMS: 556 [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-d7991d18604c44dd953fbb1a6a19061d
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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