Tetrabutylammonium Fluoride → HCID 11215446, compound

HRID 2099767Notes

Reaction equation

HRID 2099767 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([CH:8]([NH:28][C:29]([N:31]2[CH2:36][CH2:35][CH:34]([N:37]3[CH2:46][C:45]4[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=4)[NH:39][C:38]3=[O:47])[CH2:33][CH2:32]2)=[O:30])[CH2:9][C:10]2[CH:18]=[C:17]([CH3:19])[C:16]3[C:12](=[CH:13][N:14](COCC[Si](C)(C)C)[N:15]=3)[CH:11]=2)[CH:5]=[CH:4][CH:3]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[Br:1][C:2]1[N:7]=[C:6]([CH:8]([NH:28][C:29]([N:31]2[CH2:32][CH2:33][CH:34]([N:37]3[CH2:46][C:45]4[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=4)[NH:39][C:38]3=[O:47])[CH2:35][CH2:36]2)=[O:30])[CH2:9][C:10]2[CH:11]=[C:12]3[C:16](=[C:17]([CH3:19])[CH:18]=2)[NH:15][N:14]=[CH:13]3)[CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium Fluoride2×HCID 57794613HCID 57794613, compound

Product 1

HCID 11215446HCID 11215446, compoundYield 61%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

To the solution of (±)-N-(1-(6-bromopyridin-2-yl)-2-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)ethyl)-4-(2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidine-1-carboxamide (197.4 mg, 0.274 mmol) in tetrahydrofuran (8 mL) was added 1M tetrabutylammonium fluoride in tetrahydrofuran (0.55 mL, 0.549 mmol, 2 equiv). The mixture was stirred under nitrogen at 60° C. for 4 h. Another 0.5 mL of TBAF was added and the mixture was stirred overnight. 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 solid residue was purified by flash column chromatography (10% methanol in methylene chloride) to afford the desired product (98 mg, 61%) as a white solid. MS (ESI) [M+H]+=588, 1H-NMR (400 MHz, CDCl3) δ 7.93 (s, 1H), 7.32-6.78 (m, 9H), 6.69 (d, J=7.6 Hz, 1H), 5.79 (d, J=7.2 Hz, 1H), 5.17 (q, J=6.8 Hz, 1H), 4.60-4.48 (m, 1H), 4.25-4.00 (m, 4H), 3.27 (dd, J=13.2 and 6.4 Hz, 1H), 3.06 (dd, J=13.6 and 8.0 Hz, 1H), 2.85 (t, J=11.4 Hz, 2H), 2.45 (s, 3H), 1.80-1.50 (m, 5H). HPLC tR=1.62 min.

Workup

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

Sources & evidence

ORD record
ord-1126bb64704d49598e0460c23d66b4f2
Source dataset
uspto-grants-2009_08
Patent number
US07569578B2

Reaction notes

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