Methyl iodide → HCID 118235741, compound

HRID 626991Notes

Reaction equation

HRID 626991 reaction equation
[F:1][CH:2]([F:38])[O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10][C:11]1[N:15]2[CH:16]=[C:17]([C:20]3[CH:21]=[N:22][C:23]([N:26]4[CH2:31][CH2:30][C:29]([CH3:36])([C:32]([O:34][CH3:35])=[O:33])[CH2:28][CH2:27]4)=[N:24][CH:25]=3)[CH:18]=[CH:19][C:14]2=[N:13][C:12]=1[CH3:37].CI.[CH3:41][Si](C)(C)N[Si](C)(C)C.[Li]>C1COCC1>[F:38][CH:2]([F:1])[O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH:10]([C:11]1[N:15]2[CH:16]=[C:17]([C:20]3[CH:25]=[N:24][C:23]([N:26]4[CH2:27][CH2:28][C:29]([CH3:36])([C:32]([O:34][CH3:35])=[O:33])[CH2:30][CH2:31]4)=[N:22][CH:21]=3)[CH:18]=[CH:19][C:14]2=[N:13][C:12]=1[CH3:37])[CH3:41]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 57426343Lithium bis(trimethylsilyl)amideHCID 72722113HCID 72722113, compound

Product 1

HCID 118235741HCID 118235741, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of Example 43 (1 g, 1.97 mmol) and methyl iodide (0.25 mL, 4.1 mmol) in THF (10 mL) was cooled under nitrogen to −78° C. and 1M lithium hexamethyldisilazane solution (8.0 mL, 8 mmol) was added dropwise. The mixture was left stirring overnight, allowing the temperature to rise slowly to ambient temperature. The reaction mixture was partitioned between EtOAc and brine. The organic layer was washed once with brine, dried over MgSO4, filtered and concentrated in vacuo, then purified by column chromatography on SiO2, eluting with EtOAc-hexane (4:1 v/v). The residue was crystallised from diethyl ether/hexane, filtered, and washed with diethyl ether/hexane, then dried, to give the title compound (0.26 g, 25%) as a white solid. δH (400 MHz, DMSO-d6) 8.63 (m, 2H), 8.35 (m, 1H), 7.56 (dd, J 7.6, 1.5 Hz, 1H), 7.50 (m, 1H), 7.43 (m, 1H), 7.34 (m, 1H), 7.28 (m, 1H), 7.16 (d, J 7.9 Hz, 1H), 7.12 (t, J 72, 76 Hz, 1H), 4.96 (m, 1H), 4.25 (m, 2H), 3.66 (s, 3H), 3.34 (m, 2H), 2.27 (s, 3H), 2.03 (m, 2H), 1.72 (d, J 7.3 Hz, 3H), 1.44 (m, 2H), 1.23 (m, 3H). LCMS (pH 10): MH+ 536, RT 2.31 minutes.

Workup

  1. waitThe mixture was left
  2. customto rise slowly to ambient temperature
  3. customThe reaction mixture was partitioned between EtOAc and brine
  4. washThe organic layer was washed once with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. custompurified by column chromatography on SiO2
  9. washeluting with EtOAc-hexane (4:1 v/v)
  10. customThe residue was crystallised from diethyl ether/hexane
  11. filtrationfiltered
  12. washwashed with diethyl ether/hexane
  13. customdried

Sources & evidence

ORD record
ord-83e6d02d91ad46b2bdcbe5d4442870e4
Source dataset
uspto-grants-2016_04
Patent number
US09309243B2

Reaction notes

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