Tetrabutylammonium Fluoride → 6-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-N-methyl-N-((2R,3S,4S,5S)-2,3,4,5,6-pentahydroxyhexyl)nicotinamide

HRID 1400875Notes

Reaction equation

HRID 1400875 reaction equation
[CH:1]1([NH:4][C:5](=[O:80])[NH:6][C:7]2[CH:78]=[CH:77][C:10]([O:11][C:12]3[CH:17]=[CH:16][N:15]=[C:14]4[CH:18]=[C:19]([C:21]5[CH:76]=[CH:75][C:24]([C:25]([N:27]([CH3:74])[CH2:28][C@@H:29]([O:66][Si](C(C)(C)C)(C)C)[C@H:30]([O:58][Si](C(C)(C)C)(C)C)[C@@H:31]([O:50][Si](C(C)(C)C)(C)C)[C@@H:32]([O:42][Si](C(C)(C)C)(C)C)[CH2:33][O:34][Si](C(C)(C)C)(C)C)=[O:26])=[CH:23][N:22]=5)[S:20][C:13]=34)=[C:9]([F:79])[CH:8]=2)[CH2:3][CH2:2]1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[CH:1]1([NH:4][C:5](=[O:80])[NH:6][C:7]2[CH:78]=[CH:77][C:10]([O:11][C:12]3[CH:17]=[CH:16][N:15]=[C:14]4[CH:18]=[C:19]([C:21]5[CH:76]=[CH:75][C:24]([C:25]([N:27]([CH3:74])[CH2:28][C@@H:29]([OH:66])[C@H:30]([OH:58])[C@@H:31]([OH:50])[C@@H:32]([OH:42])[CH2:33][OH:34])=[O:26])=[CH:23][N:22]=5)[S:20][C:13]=34)=[C:9]([F:79])[CH:8]=2)[CH2:2][CH2:3]1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 866585946-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-N-methyl-N-((2R,3S,4S,5S)-2,3,4,5,6-pentakis(tert-butyldimethyl silyloxy)hexyl)nicotinamide

Product 1

HCID 674405406-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-N-methyl-N-((2R,3S,4S,5S)-2,3,4,5,6-pentahydroxyhexyl)nicotinamideYield 7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 243 (250 mg, 0.228 mmol) in THF (5 mL) was added TBAF (1.0M in THF) (0.273 mL, 0.273 mmol) and the reaction mixture was stirred for 2 hr at RT before concentration. The residue was purified by Biotage, (MeOH/DCM, 20-50%, SNAP 25 g cartridge) and Gilson (Phenomenex, Luna, 15μ, C18(2) 100A, 250×50.00 mm, 15 μm, 0.05% of formic acid in both MeOH/H2O, 40-90%, flow=30 mL/min), to afford title compound 244 (10 mg, 0.016 mmol, 7% yield) as a white solid. 1H NMR (400 MHz, CD3OD) δ (ppm): 8.72 (d, 1H, J=3.9 Hz), 8.47 (s, br, 1H), 8.19-8.13 (m, 2H), 8.13-8.00 (m, 1H), 7.65 (dd, 1H, J1=2.5 Hz, J2=13.1 Hz), 7.29 (t, 1H, J=8.81 Hz), 7.20-7.17 (m, 1H), 6.64 (d, 1H, J=5.3 Hz), 4.20-4.18 (m, 0.45H), 4.07-4.04 (m, 0.55H), 3.83-3.53 (m, 7H), 3.17 (s, 3H), 2.62-2.57 (m, 1H), 0.78-0.73 (m, 2H), 0.54-0.50 (m, 2H). MS: 642.6 (MH+).

Workup

  1. customThe residue was purified by Biotage, (MeOH/DCM, 20-50%, SNAP 25 g cartridge) and Gilson (Phenomenex, Luna, 15μ, C18(2) 100A, 250×50.00 mm, 15 μm, 0.05% of formic acid in both MeOH/H2O, 40-90%, flow=30 mL/min),

Sources & evidence

ORD record
ord-4ab2e1de5f9e4989ba0fb837bd555dc6
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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