Methyl iodide → HCID 58529823, compound

HRID 1972816Notes

Reaction equation

HRID 1972816 reaction equation
[CH2:1]([N:8]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([C:17]3[CH:18]=[C:19]([CH:27]4[O:32][CH2:31][CH2:30][NH:29][CH2:28]4)[N:20]4[C:25]=3[C:24]([NH2:26])=[N:23][CH:22]=[N:21]4)[CH:13]=[CH:14]2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CI.[C:35](=O)([O-])[O-].[K+].[K+]>CN(C=O)C.CCOC(C)=O>[NH3:8].[CH2:1]([N:8]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([C:17]3[CH:18]=[C:19]([CH:27]4[O:32][CH2:31][CH2:30][N:29]([CH3:35])[CH2:28]4)[N:20]4[C:25]=3[C:24]([NH2:26])=[N:23][CH:22]=[N:21]4)[CH:13]=[CH:14]2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 58529811HCID 58529811, compound

Product 2

HCID 222AmmoniaHCID 58529823HCID 58529823, compoundYield 67.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 5-(2-benzyl-2H-indazol-6-yl)-7-morpholin-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-amine (65 mg, 0.12 mmol) in DMF (2 mL) was cooled to −40° C. and treated with methyl iodide (20.5 mg, 0.145 mmol) as a solution in DMF (1 mL) and potassium carbonate (33 mg, 0.24 mmol). The reaction was allowed to warm slowly to rt over 1 h. The reaction was diluted with EtOAc and washed 3 times with water. The organic layer was dried with sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography eluting with CH2Cl2:MeOH:NH3 to provide 17.9 mg (34%) of the desired product. 1H NMR (300 MHz, DMSO-d6) δ 8.55 (s, 1 H), 7.89 (s, 1 H), 7.79 (d, 1 H, J=9 Hz), 7.65 to 7.73 (m, 1H), 7.59 (s, 1H), 7.26 to 7.41 (m, 5H), 7.13 (d, 1 H, J=9 Hz), 6.76 (s, 1H), 5.65 (s, 2H), 4.98 (dd, 1H, J=11, 2 Hz), 4.08 (dd, 1H, J=6, 2 Hz), 3.85 to 3.94 (m, 1H), 3.15 to 3.23 (m, 1H), 2.98 to 3.08 (m, 1H), 2.80-2.96 (m, 2H), 2.11 (s, 3H); ES-MS m/z 440.4 [M+H]+, HPLC RT (min) 2.07.

Workup

  1. washwashed 3 times with water
  2. dry with materialThe organic layer was dried with sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by silica gel chromatography
  5. washeluting with CH2Cl2

Sources & evidence

ORD record
ord-937a9d8e6ea54e9fb81c79e4a83e7788
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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