Methyl iodide → HCID 56848037, compound

HRID 1038304Notes

Reaction equation

HRID 1038304 reaction equation
[F:1][C:2]([F:38])([F:37])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:14]=[N:13][C:12]([C:15]3[CH:36]=[CH:35][C:18]([CH2:19][NH:20][O:21][C@H:22]4[C@H:27]([O:28][CH3:29])[C@H:26]([O:30][CH3:31])[C@@H:25]([O:32][CH3:33])[C@H:24]([CH3:34])[O:23]4)=[CH:17][CH:16]=3)=[N:11]2)=[CH:6][CH:5]=1.[CH:39](N(C(C)C)CC)(C)C.CI>O1CCCC1.O>[CH3:39][N:20]([CH2:19][C:18]1[CH:35]=[CH:36][C:15]([C:12]2[N:13]=[CH:14][N:10]([C:7]3[CH:8]=[CH:9][C:4]([O:3][C:2]([F:1])([F:37])[F:38])=[CH:5][CH:6]=3)[N:11]=2)=[CH:16][CH:17]=1)[O:21][C@H:22]1[C@H:27]([O:28][CH3:29])[C@H:26]([O:30][CH3:31])[C@@H:25]([O:32][CH3:33])[C@H:24]([CH3:34])[O:23]1

Participants

6

Reactant 3

HCID 6328Methyl iodide2×HCID 81531DiisopropylethylamineHCID 56847989HCID 56847989, compound

Product 1

HCID 56848037HCID 56848037, compoundYield 63%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-{4-[1-(4-trifluoromethoxyphenyl)-1 H-[1 ,2,4]triazol-3-yl]-benzyl}O-((2S ,3R,4R,5S ,6S)-3 ,4 ,5-trimethoxy-6-methyl-tetrahydropyran-2-yl)-hydroxylamine. (3; 205 mg, 0.38 mmol) in tetrahydrofuran (THF; 10 mL) was added diisopropylethylamine (DIEA; 300 μL, 1.7 mmol) followed by methyl iodide (250 μL, 4.0 mmol). This solution was heated to reflux. After 1 h, due to apparent precipitation of quaternized DIEA, anhydrous potassium carbonate (K2CO3) was added to the mixture along with methyl iodide (200 μL, 3.2 mmol), and the suspension was allowed to stir at reflux an additional 21 h. The mixture was then cooled to room temperature, diluted with H2O and extracted with EtOAc (2×). The organic fractions were combined, washed with brine, dried with anhydrous Na2SO4 and evaporated at room temperature under vacuum. The resulting crude material was purified by silica gel chromatography (eluting with 60% EtOAc in Hexane). The title product (131 mg, 63%) was isolated as a pale yellow solid: mp 93-100° C.; 1H NMR (400 MHz, CDCl3) δ 8.63 (d, J=4.1 Hz, 1H), 8.16 (d, J=8.3 Hz, 2H), 7.88-7.75 (m, 2H), 7.52 (t, J=10.7 Hz, 2H), 7.39 (t, J=9.5 Hz, 2H), 4.37 (d, J=13.2 Hz, 2H), 3.98-2.89 (m, 15H), 1.25 (dd, J=24.7, 6.2 Hz, 3H); ESIMS m/z 553 (M+H).

Workup

  1. temperatureThis solution was heated to reflux
  2. customdue to apparent precipitation of quaternized DIEA, anhydrous potassium carbonate (K2CO3)
  3. temperatureat reflux an additional 21 h
  4. extractionextracted with EtOAc (2×)
  5. washwashed with brine
  6. dry with materialdried with anhydrous Na2SO4
  7. customevaporated at room temperature under vacuum
  8. customThe resulting crude material was purified by silica gel chromatography (eluting with 60% EtOAc in Hexane)

Sources & evidence

ORD record
ord-4df38da0db8e47878c8af5b941875bbd
Source dataset
uspto-grants-2013_10
Patent number
US08551914B2

Reaction notes

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