Sodium Carbonate → HCID 5329380, compound

HRID 1375432Notes

Reaction equation

HRID 1375432 reaction equation
I[C:2]1[C:3](=[O:12])[NH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.C(OC([N:20]1[C:28]2[C:23](=[CH:24][C:25]([S:29]([N:32]3[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]3)(=[O:31])=[O:30])=[CH:26][CH:27]=2)[CH:22]=[C:21]1B(O)O)=O)(C)(C)C.[Cl-].[Li+].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:38][N:35]1[CH2:36][CH2:37][N:32]([S:29]([C:25]2[CH:24]=[C:23]3[C:28](=[CH:27][CH:26]=2)[NH:20][C:21]([C:2]2[C:3](=[O:12])[NH:4][C:5]4[C:10]([CH:11]=2)=[CH:9][CH:8]=[CH:7][CH:6]=4)=[CH:22]3)(=[O:31])=[O:30])[CH2:33][CH2:34]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 114145753-iodo-1H-quinolin-2-oneHCID 573504271H-Indole-1-carboxylic acid, 2-borono-5-[(4-methyl-1-piperazinyl)sulfonyl]-, 1-(1,1-dimethylethyl) ester2×

Product 1

HCID 5329380HCID 5329380, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A solution of 3-iodo-1H-quinolin-2-one (1-3, 1.50 g, 5.53 mmol, 1 equiv), 1-(tert-butoxycarbonyl)-5-[(4-methylpiperazin-1-yl)sulfonyl]-1H-indol-2-ylboronic acid (1-10, 2.00 g, 4.72 mmol, 0.854 equiv), lithium chloride (0.704 g, 16.6 mmol, 3.00 equiv), tetrakis(triphenylphosphine)palladium (0.320 g, 0.277 mmol, 0.050 equiv), and aqueous sodium carbonate solution (2 M, 13.8 mL, 27.6 mmol, 5.00 equiv) in dioxane (50 mL) was heated at 90° C. for 1 hour. 1-(tert-Butoxycarbonyl)-5-[(4-methylpiperazin-1-yl)sulfonyl]-1H-indol-2-ylboronic acid (1-10, 2.00 g total, 4.72 mmol, 0.854 equiv) was then added in two equal portions to the reaction mixture with a 30 minute interval in between additions. Following the last addition, the mixture was heated for 30 minutes. The mixture was then partitioned between brine (150 mL) and EtOAc (2×150 mL). The combined organic layers were dried over sodium sulfate and concentrated. A solution of the residue in dichloromethane (100 mL) was treated with trifluoroacetic acid (100 mL), and the resulting mixture was stirred for 45 minutes, then concentrated. The residue was purified by reverse-phase liquid chromotography (H2O/CH3CN gradient w/0.1% TFA present) to give 3-{5-[(4-methylpiperazin-1-yl)sulfonyl]-1H-indol-2-yl}quinolin-2(1H)one (1-11) as a yellow solid. 1H NMR (500 MHz, DMSO-d6) δ 12.26 (s, 1H), 12.15 (s, 1H), 8.62 (s, 1H), 8.04 (br s, 1H), 7.77 (m, 2H), 7.56 (t, 1H, J=7.6 Hz), 7.52 (s, 1H), 7.46 (d, 1H) J=8.5 Hz), 7.40 (d, 1H, J=8.1 Hz), 7.28 (t, 1H, J=7.6 Hz), 3.20–2.00 (br m, 11H).

Workup

  1. additionthe last addition
  2. temperaturethe mixture was heated for 30 minutes
  3. customThe mixture was then partitioned between brine (150 mL) and EtOAc (2×150 mL)
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. concentrationconcentrated
  6. additionA solution of the residue in dichloromethane (100 mL) was treated with trifluoroacetic acid (100 mL)
  7. concentrationconcentrated
  8. customThe residue was purified by reverse-phase liquid chromotography (H2O/CH3CN gradient w/0.1% TFA present)

Sources & evidence

ORD record
ord-fd7e65b41be4498a86ba4411ce9e2067
Source dataset
uspto-grants-2007_01
Patent number
US07169788B2

Reaction notes

Loading…