Methyl iodide → HCID 118159549, compound

HRID 628452Notes

Reaction equation

HRID 628452 reaction equation
[CH2:1]([N:8]1[C:12]2[CH:13]=[C:14]([NH:21][C:22](=O)OC(C)(C)C)[C:15]3[N:16]([C:17]([CH3:20])=[N:18][N:19]=3)[C:11]=2[CH:10]=[C:9]1[CH3:29])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].CI.C(N1C2C=C(N(C)C(=O)OC(C)(C)C)C3N(C(C)=NN=3)C=2C=C1C)C1C=CC=CC=1.FC(F)(F)C(O)=O>O1CCCC1.C(OCC)(=O)C.O>[CH2:1]([N:8]1[C:12]2[CH:13]=[C:14]([NH:21][CH3:22])[C:15]3[N:16]([C:17]([CH3:20])=[N:18][N:19]=3)[C:11]=2[CH:10]=[C:9]1[CH3:29])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 5

HCID 6328Methyl iodide2×HCID 6422Trifluoroacetic acidHCID 24758Sodium hydride2×HCID 118177584HCID 118177584, compoundHCID 131735353HCID 131735353, compound

Product 1

HCID 118159549HCID 118159549, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of tert-butyl (6-benzyl-1,7-dimethyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyridin-4-yl)carbamate (9.0 mg, 0.023 mmol, Example 248) in tetrahydrofuran (1 mL) at 0° C. was added NaH (60% in mineral oil, 2.4 mg, 0.060 mmol). After 30 minutes, a solution of methyl iodide (2.9 μL, 0.046 mmol, Aldrich) in THF (95 μL) was added to the reaction mixture, and the reaction mixture was stirred overnight, after which time additional NaH (60% in mineral oil, 8.3 mg, 0.21 mmol) and a solution of methyl iodide (5.8 μL in 0.19 mL THF, 0.092 mmol) were added. After 4 hours, water and ethyl acetate were added. Layers were separated, and the organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated. The crude tert-butyl (6-benzyl-1,7-dimethyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyridin-4-yl)(methyl)carbamate was treated with Trifluoroacetic Acid (2.0 mL, 26 mmol) for 1 hour. The solvent was removed in vacuo, and the title product was isolated by preparative HPLC-MS (Waters XBridge C18, eluting with a gradient of MeCN/H2O containing 0.15% NH4OH). Yield: (2.5 mg, 36%).

Workup

  1. waitAfter 4 hours
  2. customLayers were separated
  3. washthe organic phase was washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-31309959a3384aa8ac311de69f6a673d
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

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