Tetrabutylammonium Fluoride → HCID 72195058, compound

HRID 1486827Notes

Reaction equation

HRID 1486827 reaction equation
C1(S([N:10]2[C:18]3[C:13](=[CH:14][C:15]([C:19]4[CH:24]=[CH:23][C:22]([N:25]5[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]5)=[CH:21][CH:20]=4)=[CH:16][CH:17]=3)[C:12]3[C:32]([C:36]#[C:37][Si](C(C)C)(C(C)C)C(C)C)=[CH:33][CH:34]=[N:35][C:11]2=3)(=O)=O)C=CC=CC=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[C:36]([C:32]1[C:12]2[C:13]3[C:18](=[CH:17][CH:16]=[C:15]([C:19]4[CH:20]=[CH:21][C:22]([N:25]5[CH2:26][CH2:27][N:28]([CH3:31])[CH2:29][CH2:30]5)=[CH:23][CH:24]=4)[CH:14]=3)[NH:10][C:11]=2[N:35]=[CH:34][CH:33]=1)#[CH:37]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 89893988HCID 89893988, compound2×

Product 1

HCID 72195058HCID 72195058, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

The precursor used in Example 43, 9-benzenesulfonyl-6-(4-(4-methylpiperazin-1-yl)phenyl)-4-((triisopropylsilyl)ethynyl)-9H-pyrido[2,3-b]indole, which was obtained in a similar fashion as the procedure of Example 37, was deprotected from both the benzenesufonyl and triisopropylsilyl group using the following procedure. Under an inert atmosphere, to a solution of 9-benzenesulfonyl-6-(4-(4-methylpiperazin-1-yl)phenyl)-4-((triisopropylsilyl)ethynyl)-9H-pyrido[2,3-b]indole (73.8 mg, 0.111 mmol) in anhydrous THF (2.8 mL, 0.05M), a solution of TBAF (1M in THF, 3 eq, 330 μL) was added dropwise. The reaction was stirred at 70° C. for 2.5 h. After cooling to R.T, the mixture was then quenched cautiously with water and brine. The aqueous layer was extracted with DCM (3×40 mL) The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The crude product was first purified by silica gel flash chromatography (DCM/MeOH 95:5 to 94:6) to afford the desired product contaminated by TBAF. A pale yellow solid was obtained in 41% yield after a double trituration of the previous mixture in MeOH and then in DCM followed by filtration. 1H NMR (300 MHz, DMSO) δ 12.07 (s, 1H), 8.59 (d, J=1.1 Hz, 1H), 8.42 (d, J=5.0 Hz, 1H), 7.76 (dd, J=8.5, 1.7 Hz, 1H), 7.59 (d, J=8.7 Hz, 1H), 7.55 (d, J=8.8 Hz, 2H), 7.28 (d, J=5.0 Hz, 1H), 7.06 (d, J=8.8 Hz, 2H), 5.09 (s, 1H), 3.25-3.09 (m, 8H), 2.24 (s, 3H); 13C NMR (101 MHz, DMSO) δ 152.29 (C), 149.93 (C), 145.94 (CH), 138.04 (C), 132.39 (C), 131.36 (C), 127.13 (CH), 126.07 (CH), 122.20 (C), 120.33 (C), 118.66 (CH), 117.79 (CH), 115.81 (CH), 114.71 (C), 111.80 (CH), 89.04 (C), 80.61 (CH), 54.55 (2CH2), 47.96 (2CH2), 45.75 (NCH3); HRMS calcd for C24H23N4 [M+H]+ 367.1917 found 367.1914.

Workup

  1. customwhich was obtained in a similar fashion as the procedure of Example 37
  2. temperatureAfter cooling to R.T
  3. customthe mixture was then quenched cautiously with water and brine
  4. extractionThe aqueous layer was extracted with DCM (3×40 mL) The combined organic layers
  5. washwere washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was first purified by silica gel flash chromatography (DCM/MeOH 95:5 to 94:6)

Sources & evidence

ORD record
ord-94d8c8e7d53f4094aa775bcc28a8e213
Source dataset
uspto-grants-2016_08
Patent number
US09428500B2

Reaction notes

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