Water → HCID 50942943, compound

HRID 2045803Notes

Reaction equation

HRID 2045803 reaction equation
[F:1][C:2]1([F:40])[CH2:7][CH2:6][CH:5]([C:8]([NH:10][CH2:11][C:12]([CH3:39])([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH2:13][CH2:14][N:15]2[C@H:20]3[CH2:21][CH2:22][C@@H:16]2[CH2:17][CH:18]([N:23]2[C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=4[N:25]=[C:24]2[CH3:32])[CH2:19]3)=[O:9])[CH2:4][CH2:3]1.[H-].[Na+].I[CH3:44].O>CN(C=O)C>[F:40][C:2]1([F:1])[CH2:7][CH2:6][CH:5]([C:8]([N:10]([CH3:44])[CH2:11][C:12]([CH3:39])([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH2:13][CH2:14][N:15]2[C@H:20]3[CH2:21][CH2:22][C@@H:16]2[CH2:17][CH:18]([N:23]2[C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=4[N:25]=[C:24]2[CH3:32])[CH2:19]3)=[O:9])[CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 50942878HCID 50942878, compound

Product 1

HCID 50942943HCID 50942943, compoundYield 8.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of the title compound from example 21 (100 mg, 0.18 mmol) in dry DMF (1.5 mL) was added sodium hydride (9 mg, 0.22 mmol) as a 60% suspension in mineral oil and the solution stirred under a nitrogen atmosphere at room temperature for 30 min. Iodomethane (0.06 mL, 0.9 mmol) was added and the reaction stirred at room temperature for 2 h. Water was added and the reaction partitioned between ethyl acetate and water. The organic layer was dried (MgSO4) and concentrated in vacuo. The residue was purified by silica gel chromatography eluting with 0-5% methanol/CH2Cl2 followed by purification by HPLC eluting with 5-70% water/acetonitrile/0.1% TFA to afford the title compound (9 mg, 7%) which was isolated as the trifluoroacetate salt.

Workup

  1. stirringthe reaction stirred at room temperature for 2 h
  2. customthe reaction partitioned between ethyl acetate and water
  3. dry with materialThe organic layer was dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel chromatography
  6. washeluting with 0-5% methanol/CH2Cl2
  7. customfollowed by purification by HPLC
  8. washeluting with 5-70% water/acetonitrile/0.1% TFA

Sources & evidence

ORD record
ord-177744bbaf5242da984ec93fb6eacc7d
Source dataset
uspto-grants-2013_11
Patent number
US08592395B2

Reaction notes

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