1-Fluoro-3-iodobenzene → HCID 86687681, compound

HRID 1473614Notes

Reaction equation

HRID 1473614 reaction equation
FC(F)(F)C(O)=O.[CH3:8][CH:9]1[CH2:14][NH:13][CH2:12][CH2:11][N:10]1[C:15]1[C:24]2[C:19](=[CH:20][C:21]([S:25]([NH:28][C:29]3[CH:34]=[CH:33][N:32]=[CH:31][N:30]=3)(=[O:27])=[O:26])=[CH:22][CH:23]=2)[CH:18]=[CH:17][N:16]=1.CC(C)([O-])C.[Na+].[F:41][C:42]1[CH:47]=[CH:46][CH:45]=[C:44](I)[CH:43]=1>O1CCOCC1>[F:41][C:42]1[CH:43]=[C:44]([N:13]2[CH2:12][CH2:11][N:10]([C:15]3[C:24]4[C:19](=[CH:20][C:21]([S:25]([NH:28][C:29]5[CH:34]=[CH:33][N:32]=[CH:31][N:30]=5)(=[O:27])=[O:26])=[CH:22][CH:23]=4)[CH:18]=[CH:17][N:16]=3)[CH:9]([CH3:8])[CH2:14]2)[CH:45]=[CH:46][CH:47]=1

Participants

5

Reactant 3

HCID 707251-Fluoro-3-iodobenzeneHCID 23676156Sodium t-butoxideHCID 86687678HCID 86687678, compound

Product 1

HCID 86687681HCID 86687681, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A vial was charged with 1-(2-methylpiperazin-1-yl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide 2,2,2-trifluoroacetate (0.037 g, 0.074 mmol), ruphos palladium(ii) phenethylamine chloride (6.06 mg, 7.42 μmol), and sodium tert-butoxide (0.029 g, 0.297 mmol). Dioxane (0.742 ml) and 1-fluoro-3-iodobenzene (0.013 ml, 0.111 mmol) were added and the reaction was flushed with argon and stirred at 100° C. for one hour. The reaction was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (RediSep Gold 40 g, gradient elution 0-10% MeOH:DCM) to afford 1-(4-(3-fluorophenyl)-2-methylpiperazin-1-yl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ=8.64-8.49 (m, 2H), 8.38-8.21 (m, 3H), 7.97 (d, J=10.1 Hz, 1H), 7.68 (d, J=5.8 Hz, 1H), 7.24 (q, J=8.2 Hz, 1H), 7.05 (br. s., 1H), 6.87-6.76 (m, 2H), 6.56 (dt, J=1.9, 8.2 Hz, 1H), 4.02 (d, J=3.1 Hz, 1H), 3.61-3.44 (m, 3H), 3.29-3.22 (m, 1H), 1.08 (d, J=6.3 Hz, 5H). m/z (ESI) 479.2 (M+H)+.

Workup

  1. customthe reaction was flushed with argon
  2. additionThe reaction was diluted with ethyl acetate
  3. washwashed with water
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. dry with materialthe combined organic layers were dried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe material was purified via column chromatography (RediSep Gold 40 g, gradient elution 0-10% MeOH:DCM)

Sources & evidence

ORD record
ord-878dafbabb844c2a9208524d11e84e96
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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