Trimethylsilyl iodide → HCID 24739634, compound

HRID 1811558Notes

Reaction equation

HRID 1811558 reaction equation
[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([O:20][CH3:21])=[C:18]([NH:22][C:23]3[C:24]([CH3:34])=[N:25][C:26]([NH:29][CH2:30][CH2:31][O:32]C)=[CH:27][CH:28]=3)[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].I[Si](C)(C)C>C(Cl)Cl>[CH:1]([O:4][C:5]([N:7]1[CH2:8][CH2:9][CH:10]([O:13][C:14]2[C:19]([O:20][CH3:21])=[C:18]([NH:22][C:23]3[C:24]([CH3:34])=[N:25][C:26]([NH:29][CH2:30][CH2:31][OH:32])=[CH:27][CH:28]=3)[N:17]=[CH:16][N:15]=2)[CH2:11][CH2:12]1)=[O:6])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 85247Trimethylsilyl iodideHCID 11503815HCID 11503815, compound

Product 1

HCID 24739634HCID 24739634, compoundYield 40.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-{5-methoxy-6-[6-(2-methoxy-ethylamino)-2-methyl-pyridin-3-ylamino]-pyrimidin-4-yloxy}-piperidine-1-carboxylic acid isopropyl ester (HCl salt, 101 mg, 0.2 mmol) in 10 mL of CH2Cl2, iodotrimethylsilane (142 μl, 1 mmol) was added at room temperature. The mixture was stirred at the same temperature. After 2 hr, the mixture was purified by HPLC and converted to HCl salt by adding 2 mL of 4M HCl in dioxane solution and concentrated to give 4-{6-[6-(2-hydroxy-ethylamino)-2-methyl-pyridin-3-ylamino]-5-methoxy-pyrimidin-4-yloxy}-piperidine-1-carboxylic acid isopropyl ester (Compound 78) (HCl salt, 37 mg, 37%). 1HNMR (CD3CN-d3, 400 MHz) δ 1.12-1.14 (d, 6H), 1.66-1.68 (m, 2H), 1.84-1.89 (m, 2H), 2.35 (s, 3H), 3.27-3.32 (m, 2H), 3.41 (s, 2H), 3.61 (s, 4H), 3.82 (s, 3H), 4.72-4.78 (m, 1H), 5.28 (m, 1H), 6.88-6.90 (m, 1H), 6.69-7.71 (m, 1H), 7.99 (s, 1H) 8.18 (s br, 1H), 8.42 (s br, 1H). Exact mass calculated for C22H32N6O5 460.24. found 461.5 (MH+).

Workup

  1. customthe mixture was purified by HPLC
  2. additionby adding 2 mL of 4M HCl in dioxane solution
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-e64f3874ba534853ad4d4011da02f2ad
Source dataset
uspto-grants-2013_01
Patent number
US08362248B2

Reaction notes

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