Methyl iodide → HCID 69311148, compound

HRID 914686Notes

Reaction equation

HRID 914686 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH2:17][CH:18]2[C:27]3[N:23]([C:24]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[N:25][N:26]=3)[C:22]3[CH:34]=[CH:35][CH:36]=[CH:37][C:21]=3[N:20]([CH2:38][C:39](=[O:50])[N:40]([CH:47]([CH3:49])[CH3:48])[C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[C:19]2=[O:51])=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:52][Si]([N-][Si](C)(C)C)(C)C.[K+].CI>CN(C=O)C.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH2:17][C:18]2([CH3:52])[C:27]3[N:23]([C:24]([C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)=[N:25][N:26]=3)[C:22]3[CH:34]=[CH:35][CH:36]=[CH:37][C:21]=3[N:20]([CH2:38][C:39](=[O:50])[N:40]([CH:47]([CH3:48])[CH3:49])[C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[C:19]2=[O:51])=[CH:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 69311002HCID 69311002, compound

Product 1

HCID 69311148HCID 69311148, compoundYield 33.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-5 °C

Procedure

To a solution of 3-{6-[(isopropyl-phenyl-carbamoyl)-methyl]-5-oxo-1-phenyl-5,6-dihydro-4H-2,3,6,10b-tetraaza-benzo[e]azulen-4-ylmethyl}-indole-1-carboxylic acid tert-butyl ester (100 mg, 0.147 mmol) in DMF (2 mL) at −5° C. was added KHMDS (0.5M in THF, 322 μL, 0.161 mmol). The solution was stirred at −5° C. for 20 minutes and methyl iodide (10 μL, 0.161 mmol) was added. The reaction was stirred at room temperature for 24 hours, was diluted with EtOAc and the organic solution was washed with brine (3×). The organic solution was dried (Na2SO4), filtered and concentrated. The residue was purified by preparative chromatography (2×) eluting with 50% EtOAc in hexanes to provide 34 mg of 3-{6-[(isopropyl-phenyl-carbamoyl)-methyl]-4-methyl-5-oxo-1-phenyl-5,6-dihydro-4H-2,3,6,10b-tetraaza-benzo[e]azulen-4-ylmethyl}-indole-1-carboxylic acid tert-butyl ester. 1H NMR (CD2Cl2) δ 8.05 (d, 1H), 7.67 (d, 1H), 7.36-7.54 (m, 10H), 7.08-7.30 (m, 6H), 6.90 (d, 1H), 5.02 (m, 1H), 4.29 (d, 1H), 4.11 (m, 1H), 2.78 (s, 2H), 1.80 (s, 3H), 1.64 (s, 9H), 1.10 (m, 6H); MS 695.3 (M+1).

Workup

  1. stirringThe reaction was stirred at room temperature for 24 hours
  2. washthe organic solution was washed with brine (3×)
  3. dry with materialThe organic solution was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by preparative chromatography (2×)
  7. washeluting with 50% EtOAc in hexanes

Sources & evidence

ORD record
ord-32bb41c45b9b4a03bd97b03fc00ead6d
Source dataset
uspto-grants-2007_09
Patent number
US07265104B2

Reaction notes

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