Triisopropyl borate → 3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-ylboronic acid

HRID 1028004노트

반응식

HRID 1028004 반응식
[CH:1]1([N:6]2[C:14]3[C:9](=[CH:10][C:11](F)=[C:12]([CH3:15])[CH:13]=3)[C:8]([C:17]#[N:18])=[CH:7]2)[CH2:5][CH2:4][CH2:3]C1.[B:19](OC(C)C)([O:24]C(C)C)[O:20]C(C)C.[Li+].[CH3:33][CH:34]([N-]C(C)C)C>C1COCC1>[C:17]([C:8]1[C:9]2[C:14](=[CH:13][C:12]([CH:15]3[CH2:34][CH2:33]3)=[CH:11][CH:10]=2)[N:6]([CH:1]2[CH2:3][CH2:4][CH2:5]2)[C:7]=1[B:19]([OH:24])[OH:20])#[N:18]

참가 물질

5

반응물 3

HCID 21531Triisopropyl borateHCID 2724682Lithium diisopropylamideHCID 667305931-cyclopentyl-5-fluoro-6-methyl-1H-indole-3-carbonitrile

생성물 1

HCID 667305423-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-ylboronic acid

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
-78 °C

실험 절차

Into a solution of 1-cyclopentyl-5-fluoro-6-methyl-1H-indole-3-carbonitrile (4.4 g, 18.2 mmol) and triisopropyl borate (7.6 mL, 33 mmol) in THF (75 mL) at −78° C. was added LDA (1.5 M in cyclohexane, 15.8 mL, 23.7 mmol). The mixture was stirred at −78° C. for 30 min, quenched with ice water (200 mL) and stirred for 15 min without cooling. The mixture was extracted with ethyl acetate 1:1 in hexane (20 mL). The aqueous layer was acidified with aq. 2 N HCl to pH 5 and then extracted with CH2Cl2 (100 mL). The organic layer was dried over Na2SO4 and concentrated to give 3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-ylboronic acid as a solid (6.2 g, 90% pure by LCMS) which was used in the next step without further purification.

후처리

  1. customquenched with ice water (200 mL)
  2. stirringstirred for 15 min
  3. temperaturewithout cooling
  4. extractionThe mixture was extracted with ethyl acetate 1:1 in hexane (20 mL)
  5. extractionextracted with CH2Cl2 (100 mL)
  6. dry with materialThe organic layer was dried over Na2SO4
  7. concentrationconcentrated

출처 및 근거

ORD 기록
ord-fee8d33d798d46e09ba7d37b41fd15ea
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08735414B2

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