Dimethylformamide → HCID 86344133, compound

HRID 1504536Notes

Reaction equation

HRID 1504536 reaction equation
Br[C:2]1[C:7]([F:8])=[CH:6][C:5]([N:9]2[C:18]3[C:13](=[CH:14][C:15]([S:19]([NH:22][C:23]4[CH:27]=[CH:26][O:25][N:24]=4)(=[O:21])=[O:20])=[CH:16][CH:17]=3)[N:12]=[CH:11][C:10]2=[O:28])=[C:4]([O:29][CH3:30])[CH:3]=1.CN(C=O)C.C(NC(C)C)(C)C.[C:43]([CH:45]1[CH2:49][CH2:48][CH2:47][CH2:46]1)#[CH:44]>CCOC(C)=O.[Cu]I.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>[CH:45]1([C:43]#[C:44][C:2]2[C:7]([F:8])=[CH:6][C:5]([N:9]3[C:18]4[C:13](=[CH:14][C:15]([S:19]([NH:22][C:23]5[CH:27]=[CH:26][O:25][N:24]=5)(=[O:20])=[O:21])=[CH:16][CH:17]=4)[N:12]=[CH:11][C:10]3=[O:28])=[C:4]([O:29][CH3:30])[CH:3]=2)[CH2:49][CH2:48][CH2:47][CH2:46]1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 7912DiisopropylamineHCID 136725CyclopentylacetyleneHCID 117737249HCID 117737249, compound

Product 1

HCID 86344133HCID 86344133, compoundYield 65%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A vial was charged with 1-(4-bromo-5-fluoro-2-methoxyphenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoxaline-6-sulfonamide (147.0 mg, 0.297 mmol), copper(i) iodide (8.48 mg, 0.045 mmol), and Pd(PPh3)4 (34.3 mg, 0.030 mmol). The vial was flushed with Ar (g), then DMF (1484 μl), N,N-diisopropylamine (423 μl, 2.97 mmol), and ethynylcyclopentane (140 mg, 1.484 mmol) were added in sequence. The vial was sealed and heated to 60° C. for 1 h. The mixture was cooled, diluted with EtOAc, washed with 2N aq. HCl (2×), dried over sodium sulfate, filtered, and concentrated. The residue was taken up in DMSO-MeOH and filtered through a 0.2 micron filter. The filtrate was purified by reverse-phase HPLC (25-75 CH3CN/H2O with 0.1% TFA). Fractions containing desired product were combined and lyophilized to give 1-(4-(cyclopentylethynyl)-5-fluoro-2-methoxyphenyl)-N-3-isoxazolyl-2-oxo-1,2-dihydro-6-quinoxalinesulfonamide (98.2 mg, 65%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ=11.74 (s, 1H), 8.75 (d, J=2.0 Hz, 1H), 8.47 (s, 1H), 8.30 (d, J=2.3 Hz, 1H), 7.90 (dd, J=2.2, 8.8 Hz, 1H), 7.48 (d, J=9.1 Hz, 1H), 7.38 (d, J=6.3 Hz, 1H), 6.95 (d, J=8.9 Hz, 1H), 6.49 (d, J=2.0 Hz, 1H), 3.67 s, 3H), 2.98 (t, J=7.3 Hz, 1H), 2.09-1.98 (m, 2H), 1.80-1.58 (m, 6H). m/z (ESI) 509.2 (M+H)+.

Workup

  1. customThe vial was flushed with Ar (g)
  2. customThe vial was sealed
  3. temperatureThe mixture was cooled
  4. washwashed with 2N aq. HCl (2×)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. filtrationfiltered through a 0.2 micron
  9. filtrationfilter
  10. customThe filtrate was purified by reverse-phase HPLC (25-75 CH3CN/H2O with 0.1% TFA)
  11. additionFractions containing desired product

Sources & evidence

ORD record
ord-1e68fcb62eb445178bd1d2d5b9ea4f86
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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