Phenylboronic Acid → tert-butyl (1-(4-(6-phenyl-9H-benzo[f]pyrido[2,3-b][1,2,4]triazolo [4,3-d][1,4]diazepin-3-yl)phenyl)cyclobutyl)carbamate

HRID 44244노트

반응식

HRID 44244 반응식
Br[C:2]1[CH:37]=[N:36][C:5]2[NH:6][C:7]3[CH:35]=[CH:34][CH:33]=[CH:32][C:8]=3[C:9]3[N:10]([C:11]([C:14]4[CH:19]=[CH:18][C:17]([C:20]5([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:23][CH2:22][CH2:21]5)=[CH:16][CH:15]=4)=[N:12][N:13]=3)[C:4]=2[CH:3]=1.[C:38]1(B(O)O)[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C(O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:38]1([C:2]2[CH:37]=[N:36][C:5]3[NH:6][C:7]4[CH:35]=[CH:34][CH:33]=[CH:32][C:8]=4[C:9]4[N:10]([C:11]([C:14]5[CH:19]=[CH:18][C:17]([C:20]6([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:29])([CH3:28])[CH3:30])[CH2:23][CH2:22][CH2:21]6)=[CH:16][CH:15]=5)=[N:12][N:13]=4)[C:4]=3[CH:3]=2)[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1

참가 물질

7

반응물 3

HCID 66827Phenylboronic AcidHCID 516892Sodium BicarbonateHCID 136163795tert-butyl (1-(4-(6-bromo-9H-benzo[f]pyrido[2,3-b][1,2,4]triazolo[4,3-d][1,4]diazepin-3-yl)phenyl)cyclobutyl)carbamate

생성물 1

HCID 136163775tert-butyl (1-(4-(6-phenyl-9H-benzo[f]pyrido[2,3-b][1,2,4]triazolo [4,3-d][1,4]diazepin-3-yl)phenyl)cyclobutyl)carbamate

시약·촉매·용매 3

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 702Ethanol용매HCID 1140Toluene용매

실험 절차

A solution of tert-butyl (1-(4-(6-bromo-9H-benzo[f]pyrido[2,3-b][1,2,4]triazolo[4,3-d][1,4]diazepin-3-yl)phenyl)cyclobutyl)carbamate (100 mg, 0.18 mmol), phenyl boronic acid (44 mg, 0.36 mmol) and tetrakis(triphenylphosphine) palladium (0) (21 mg, 0.018 mmol) in toluene (2 mL), ethanol (2 mL and saturated aqueous sodium bicarbonate (0.2 mL) was stirred at 100° C. for 6 hours. The mixture was partitioned between ethyl acetate (80 mL) and water (30 mL). The phases were separated and the organic phase was washed with brine (30 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography (SiO2, 25% ethyl acetate in dichloromethane). The tert-butyl (1-(4-(6-phenyl-9H-benzo[f]pyrido[2,3-b][1,2,4]triazolo [4,3-d][1,4]diazepin-3-yl)phenyl)cyclobutyl)carbamate was obtained as a white solid (60 mg). M.p.=140-142° C.; 400 M Hz 1H NMR (DMSO-d6) δ: 8.94 (br.s, 1H), 8.44 (br.s, 1H), 7.98 (d, J=8.0 Hz, 1H), 7.75 (br.s, 1H), 7.65-7.40 (m, 6H), 7.38-7.24 (m, 4H), 7.15 (t, J=7.4 Hz, 1H), 7.04-6.96 (m, 2H), 2.48-2.30 (m, 4H), 2.10-1.90 (m, 1H), 1.85-1.75 (m, 1H), 1.33 (s, 9H); LCMS[M+H]: 557.

후처리

  1. customThe mixture was partitioned between ethyl acetate (80 mL) and water (30 mL)
  2. customThe phases were separated
  3. washthe organic phase was washed with brine (30 mL)
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by flash chromatography (SiO2, 25% ethyl acetate in dichloromethane)

출처 및 근거

ORD 기록
ord-ae221e9c22d7442ba87abf99e8eb56e6
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08541407B2

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