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 44244ノート

反応式

HRID 44244 の反応式
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

参加物

7

反応物 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

生成物 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

試薬・触媒・溶媒 3

HCID 11979704Tetrakis(triphenylphosphine)palladium触媒HCID 702Ethanol溶媒HCID 1140Toluene溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-ae221e9c22d7442ba87abf99e8eb56e6
出典データセット
uspto-grants-2013_09
特許番号
US08541407B2

反応ノート

読み込み中…