Tetrabutylammonium Fluoride → 3-[1-[3-(4-ethyl-2-pyridinyl)-4-(7-methyl-1H-indazol-5-yl)butanoyl]piperidin-4-yl]-1,4-dihydroquinazolin-2-one

HRID 2099757Notes

Reaction equation

HRID 2099757 reaction equation
[CH2:1]([C:3]1[CH:8]=[CH:7][N:6]=[C:5]([CH:9]([CH2:30][C:31]2[CH:39]=[C:38]([CH3:40])[C:37]3[C:33](=[CH:34][N:35](COCC[Si](C)(C)C)[N:36]=3)[CH:32]=2)[CH2:10][C:11]([N:13]2[CH2:18][CH2:17][CH:16]([N:19]3[CH2:28][C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[NH:21][C:20]3=[O:29])[CH2:15][CH2:14]2)=[O:12])[CH:4]=1)[CH3:2].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[CH2:1]([C:3]1[CH:8]=[CH:7][N:6]=[C:5]([CH:9]([CH2:30][C:31]2[CH:32]=[C:33]3[C:37](=[C:38]([CH3:40])[CH:39]=2)[NH:36][N:35]=[CH:34]3)[CH2:10][C:11]([N:13]2[CH2:14][CH2:15][CH:16]([N:19]3[CH2:28][C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[NH:21][C:20]3=[O:29])[CH2:17][CH2:18]2)=[O:12])[CH:4]=1)[CH3:2]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 57794597(+/-)-3-(1-(3-(4-Ethylpyridin-2-yl)-4-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)butanoyl)piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-one

Product 1

HCID 111918903-[1-[3-(4-ethyl-2-pyridinyl)-4-(7-methyl-1H-indazol-5-yl)butanoyl]piperidin-4-yl]-1,4-dihydroquinazolin-2-oneYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

To the solution of (±)-3-(1-(3-(4-ethylpyridin-2-yl)-4-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)butanoyl)piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-one (69 mg, 0.103 mmol) in tetrahydrofuran (2 mL) was added 1M tetrabutylammonium fluoride in tetrahydrofuran (0.21 mL, 0.207 mmol, 2 equiv). The mixture was stirred at 60° C. under nitrogen for 4 h. Tetrahydrofuran was removed in vacuo and the residue was partitioned between water and ethyl acetate. The layers were separated and the organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash column chromatography (10% methanol in methylene chloride) to afford the desired product (50.3 mg, 91%) as a white powder: MS (ESI) [M+H]+=537. 1H-NMR (400 MHz, CDCl3) δ 8.48-8.42 (m, 1H), 7.95-7.91 (m, 2H), 7.22-7.10 (m, 2H), 7.06-6.60 (m, 6H), 4.70-4.64 (m, 1H), 4.60-4.42 (m, 1H), 4.24-3.90 (m, 3H), 3.78-3.60 (m, 1H), 3.26-2.92 (m, 3H), 2.92-2.38 (m, 8H), 1.78-1.50 (m, 3H), 1.50-1.12 (m, 2H), 1.12-0.94 (m, 3H).

Workup

  1. customTetrahydrofuran was removed in vacuo
  2. customthe residue was partitioned between water and ethyl acetate
  3. customThe layers were separated
  4. washthe organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography (10% methanol in methylene chloride)

Sources & evidence

ORD record
ord-bf017d50c03c4af69e0ea0dc230f4080
Source dataset
uspto-grants-2009_08
Patent number
US07569578B2

Reaction notes

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