Ethanol → HCID 136390286, compound

HRID 1046981Notes

Reaction equation

HRID 1046981 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][C:21]([O:23]C)=[O:22].C(O)C.C(=O)(O)[O-].[Na+].CC1(C)C(C)(C)OB([C:41]2[CH:46]=[CH:45][C:44]([C:47]3([NH:51][C:52](=[O:58])[O:53][C:54]([CH3:57])([CH3:56])[CH3:55])[CH2:50][CH2:49][CH2:48]3)=[CH:43][CH:42]=2)O1>C1(C)C=CC=CC=1>[C:54]([O:53][C:52]([NH:51][C:47]1([C:44]2[CH:45]=[CH:46][C:41]([C:2]3[N:6]4[C:7]5[CH:19]=[CH:18][CH:17]=[N:16][C:8]=5[NH:9][C:10]5[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=5[C:5]4=[N:4][C:3]=3[CH2:20][C:21]([OH:23])=[O:22])=[CH:42][CH:43]=2)[CH2:50][CH2:49][CH2:48]1)=[O:58])([CH3:57])([CH3:55])[CH3:56]

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 136390253HCID 136390253, compound

Product 1

HCID 136390286HCID 136390286, compoundYield 19.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of methyl 2-(3-bromo-9H-benzo[f]imidazo[1,2-d]pyrido[2,3-b][1,4]diazepin-2-yl)acetate (0.15 g, 1 eq.) in a mixture of toluene (8 mL), ethanol (8 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 (0.219 g, 1.5 eq.). The reaction was degassed (nitrogen) for 5 minutes and tetrakis(triphenylphosphine)palladium(0) added (0.045 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 (30 mL). The aqueous phase was extracted with dichloromethane (2×30 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 (0-100% ethyl acetate in hexanes) gave 2-(3-(4-(1-((tert-butoxycarbonyl)amino)cyclobutyl)phenyl)-9H-benzo[f]imidazo[1,2-d]pyrido[2,3-b][1,4]diazepin-2-yl)acetic acid (0.04 g, 19%). LCMS: 538 [M+H].

Workup

  1. customThe reaction was degassed (nitrogen) for 5 minutes
  2. additiontetrakis(triphenylphosphine)palladium(0) added (0.045 g)
  3. customThe reaction was again degassed for 5 minutes
  4. temperatureThe reaction mixture was cooled to room temperature
  5. additionpoured onto water (30 mL)
  6. extractionThe aqueous phase was extracted with dichloromethane (2×30 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 (0-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-c79d2cee6fb44183bfedce932ba93136
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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