Triisopropyl borate → HCID 68288695, compound

HRID 526068Notes

Reaction equation

HRID 526068 reaction equation
[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[CH:15]=[C:14]([C:16]([NH:18][C:19]2[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=2)=[O:17])[C:13]2[C:8](=[CH:9][CH:10]=[C:11](C3C=CC=CC=3)[CH:12]=2)[N:7]=1.[Li]CCCC.C([O:39][B:40](OC(C)C)[O:41]C(C)C)(C)C.CO.ClCCl>C1COCC1>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[CH:15]=[C:14]([C:16](=[O:17])[NH:18][C:19]2[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=2)[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([B:40]([OH:41])[OH:39])[CH:12]=2)[N:7]=1

Participants

6

Reactant 4

HCID 21531Triisopropyl borateHCID 21226129Dichloromethane methanolHCID 49790728HCID 49790728, compound2×HCID 178418339Butyllithium

Product 1

HCID 68288695HCID 68288695, compoundYield 81.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

6-bromo-2-(furan-2-yl)-N-(pyridin-3-yl)quinoline-4-carboxamide (0.4 g, prepared as described above for compound 1) was dissolved in THF (15 ml) in a round-bottomed flask under argon atmosphere. The solution was cooled to −78° C., then n-BuLi (15% in hexanes, 1.0 ml, 1.5 eq) was added dropwise. The reaction was maintained at this temperature for 45 minutes, at which time triisopropylborate (0.376 g, 2.0 eq.) was added dropwise. The reaction was allowed to warm to RT and stirred for an additional 3 hours. The completion of the reaction was monitored on TLC using methanol:dichloromethane (1:9) as a mobile phase. After completion of the reaction, the reaction mixture was quenched with saturated NH4Cl solution (10 ml), then was extracted with ethyl acetate (2*10 ml) which was discarded. The aqueous layer was added Conc.HCl to adjust pH up to 6-7. The solid was precipitated which further was filtered on Buckner funnel and washed with water (10 ml). The solid was dried to obtain (2-(furan-2-yl)-4-(pyridin-3-ylcarbamoyl)quinolin-6-yl)boronic acid (0.300 g) which was used as such in next step.

Workup

  1. additionwas added dropwise
  2. temperatureto warm to RT
  3. customAfter completion of the reaction
  4. customthe reaction mixture was quenched with saturated NH4Cl solution (10 ml)
  5. extractionwas extracted with ethyl acetate (2*10 ml) which
  6. additionThe aqueous layer was added Conc
  7. customThe solid was precipitated which
  8. filtrationfurther was filtered on Buckner funnel
  9. washwashed with water (10 ml)
  10. customThe solid was dried

Sources & evidence

ORD record
ord-a1e88710433542e998b2d597fed70235
Source dataset
uspto-grants-2016_05
Patent number
US09345700B2

Reaction notes

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