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 44244Notes

Reaction equation

HRID 44244 reaction equation
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

Participants

7

Reactant 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

Product 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

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-ae221e9c22d7442ba87abf99e8eb56e6
Source dataset
uspto-grants-2013_09
Patent number
US08541407B2

Reaction notes

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