Sodium Carbonate → HCID 5329381, compound

HRID 1375435Notes

Reaction equation

HRID 1375435 reaction equation
C(OC([N:8]1[C:16]2[C:11](=[CH:12][C:13]([S:17]([N:20]3[CH2:25][CH2:24][N:23](C(OC(C)(C)C)=O)[CH2:22][CH2:21]3)(=[O:19])=[O:18])=[CH:14][CH:15]=2)[CH:10]=[C:9]1B(O)O)=O)(C)(C)C.I[C:37]1[C:38](=[O:47])[NH:39][C:40]2[C:45]([CH:46]=1)=[CH:44][CH:43]=[CH:42][CH:41]=2.[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>[N:20]1([S:17]([C:13]2[CH:12]=[C:11]3[C:16](=[CH:15][CH:14]=2)[NH:8][C:9]([C:37]2[C:38](=[O:47])[NH:39][C:40]4[C:45]([CH:46]=2)=[CH:44][CH:43]=[CH:42][CH:41]=4)=[CH:10]3)(=[O:19])=[O:18])[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 114145753-iodo-1H-quinolin-2-oneHCID 21963088{1-(tert-Butoxycarbonyl)-5-[4-(tert-butoxycarbonyl)piperazine-1-sulfonyl]-1H-indol-2-yl}boronic acid

Product 1

HCID 5329381HCID 5329381, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

1-(tert-Butoxycarbonyl)-5-{[4-(tert-butoxycarbonyl)piperazin-1-yl]sulfonyl}-1H-indol-2-ylboronic acid (2-3, 1.88 g, 3.69 mmol, 2.0 equiv) was added in four equal portions at 30 minute intervals to a solution of 3-iodo-1H-quinolin-2-one (1-3, 0.500 g, 1.84 mmol, 1 equiv), lithium chloride (0.235 g, 5.54 mmol, 3.00 equiv), tetrakis(triphenylphosphine)palladium (0.107 g, 0.093 mmol, 0.050 equiv), and aqueous sodium carbonate solution (2 M, 4.61 mL, 9.22 mmol, 5.00 equiv) in dioxane (50 mL) at 90° C. The reaction mixture was heated for 2 h at 90° C. following the final addition. The mixture was then partitioned between brine (100 mL) and EtOAc (2×100 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-(piperazin-1-ylsulfonyl)-1H-indol-2-yl]quinolin-2(1H)-one (2-4) as a yellow solid. 1H NMR (500 MHz, DMSO-d6) δ 12.23 (br s, 1H), 12.11 (s, 1H), 8.62 (s, 1H), 8.00 (br s, 1H), 7.77 (d, 1H, J=7.8 Hz), 7.74 (d, 1H, J=8.6 Hz), 7.56 (t, 1H, J=7.8 Hz), 7.51 (s, 1H), 7.44 (d, 1H, J=8.6 Hz), 7.40 (d, 1H, J=8.1 Hz), 7.27 (t, 1H, J=7.8 Hz), 2.77 (m, 4H), 2.71 (m, 4H).

Workup

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

Sources & evidence

ORD record
ord-e19ccf435d3241d685e475346cc35fea
Source dataset
uspto-grants-2007_01
Patent number
US07169788B2

Reaction notes

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