2-Thiopheneboronic acid → HCID 69957093, compound

HRID 1940823Notes

Reaction equation

HRID 1940823 reaction equation
Br[C:2]1[CH:33]=[CH:32][CH:31]=[CH:30][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]([N:15]2[C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=3[CH2:19][N:18]3[CH:26]=[CH:27][CH:28]=[C:17]3[CH2:16]2)=[O:14])=[C:9]([Cl:29])[CH:8]=1)=[O:5].[S:34]1[CH:38]=[CH:37][CH:36]=[C:35]1B(O)O.O.O.O.O.O.O.O.O.[OH-].[Ba+2].[OH-]>COCCOC.O.[Pd](Cl)Cl.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>[Cl:29][C:9]1[CH:8]=[C:7]([NH:6][C:4](=[O:5])[C:3]2[CH:30]=[CH:31][CH:32]=[CH:33][C:2]=2[C:35]2[S:34][CH:38]=[CH:37][CH:36]=2)[CH:12]=[CH:11][C:10]=1[C:13]([N:15]1[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=2[CH2:19][N:18]2[CH:26]=[CH:27][CH:28]=[C:17]2[CH2:16]1)=[O:14]

Participants

7

Reactant 3

HCID 27339602-Thiopheneboronic acid2×HCID 17749109Barium hydroxide, octahydrateHCID 54446869HCID 54446869, compound

Product 1

HCID 69957093HCID 69957093, compoundYield 135.5%

Reagents, catalysts & solvents 3

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalyst2×HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

The 2-bromo-N-[3-chloro-4-(10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-10-carbonyl)-phenyl]benzamide (1.04 g, 2.0 mmol) and thiophene-2-boronic acid (0.32 g, 2.4 mmol), and barium hydroxide octahydrate (0.88 g, 2.8 mmol) was suspended in ethylene glycol dimethyl ether (28.8 ml) and water (4.8 ml). The heterogeneous mixture was stirred at room temperature and purged with nitrogen for ten minutes before bis(triphenylphosphine) palladium (II) chloride (0.17 g, 0.24 mmol) was added. The reaction was capped with a nitrogen balloon and heated in an oil bath at 70° C. After 20 hours, additional thiophene-2-boronic acid (0.13 g, 1 mmol) was added to the reaction. After 24 hours additional bis(triphenylphosphine)-palladium(II)chloride (84 mg, 0.12 mmol) was added to the reaction flask. The reaction was cooled to room temperature and the mixture was extracted into benzene. The combined organic extracts were washed with brine, dried (MgSO4), filtered and concentrated in vacuo to yield a brown solid (1.42 g). The solid was triturated with ethyl acetate and filtered. The filtrate was purified by flash chromatography using silica gel with hexane-ethyl acetate (1:1) as the mobile phase to afford a pale yellow solid (0.59 g, 56%), which was dried under vacuum at 78° C. for two days, m.p. 132°-136° C. MS (EI),m/z: 523 (M+).

Workup

  1. additionwas added
  2. customThe reaction was capped with a nitrogen balloon
  3. temperatureheated in an oil bath at 70° C
  4. temperatureThe reaction was cooled to room temperature
  5. extractionthe mixture was extracted into benzene
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8b47b36e0b664aadb3c577528e6d19a5
Source dataset
uspto-grants-1997_12
Patent number
US05700796

Reaction notes

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