Trimethylsilyl iodide → HCID 86267613, compound

HRID 709994Notes

Reaction equation

HRID 709994 reaction equation
[CH:1]([NH:4][C:5]1[N:10]=[C:9]([O:11]C)[C:8]([C:13]2[N:18]=[CH:17][C:16]([O:19][C:20]3[CH:25]=[CH:24][N:23]=[C:22]([C:26]([NH:28][CH3:29])=[O:27])[CH:21]=3)=[CH:15][CH:14]=2)=[CH:7][N:6]=1)([CH3:3])[CH3:2].I[Si](C)(C)C.C(Cl)Cl.C1COCC1>ClCCCl>[CH:1]([NH:4][C:5]1[NH:10][C:9](=[O:11])[C:8]([C:13]2[N:18]=[CH:17][C:16]([O:19][C:20]3[CH:25]=[CH:24][N:23]=[C:22]([C:26]([NH:28][CH3:29])=[O:27])[CH:21]=3)=[CH:15][CH:14]=2)=[CH:7][N:6]=1)([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 85247Trimethylsilyl iodide2×HCID 21919333Tetrahydrofurane dichloromethaneHCID 90417743HCID 90417743, compound

Product 1

HCID 86267613HCID 86267613, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 4-((6-(2-(isopropylamino)-4-methoxypyrimidin-5-yl)pyridin-3-yl)oxy)-N-methylpicolinamide (0.072 g, 0.183 mmol) in DCE (10 mL) was treated with iodotrimethylsilane (0.497 mL, 3.65 mmol), heated at 50° C. for 20 h, treated with additional iodotrimethylsilane (0.25 mL, 1.84 mmol) and heated at 60° C. for 20 h. The mixture was cooled to RT, treated with DCM/THF (5:1), washed with satd. NaHCO3, 10% sodium bisulfite, then brine. The combined aqueous washes were back-extracted with DCM/THF (5:1) (1×) and the combined organics were dried over Na2SO4, concentrated to dryness and purified by preparatory TLC (EtOAc) to afford 4-((6-(2-(isopropylamino)-6-oxo-1,6-dihydropyrimidin-5-yl)pyridin-3-yl)oxy)-N-methylpicolinamide (16 mg, 23%). 1H NMR (400 MHz, DMSO-d6): δ 10.89 (br s, 1H), 8.79 (d, J=5.2 Hz, 1H), 8.66 (s, 1H), 8.52 (d, J=5.6 Hz, 1H), 8.47 (d, J=2.9 Hz, 1H), 8.44 (d, J=8.8 Hz, 1H), 7.67 (dd, J=8.8, 2.9 Hz, 1H), 7.42 (d, J=2.6 Hz, 1H), 7.21 (dd, J=5.6, 2.6 Hz, 1H), 6.74 (br s, 1H), 4.08 (m, 1H), 2.77 (d, J=4.8 Hz, 3H), 1.16 (d, J=6.5 Hz, 6H); MS (ESI) m/z: 381.2 (M+H+).

Workup

  1. temperatureheated at 60° C. for 20 h
  2. temperatureThe mixture was cooled to RT
  3. washwashed with satd
  4. extractionThe combined aqueous washes were back-extracted with DCM/THF (5:1) (1×)
  5. dry with materialthe combined organics were dried over Na2SO4
  6. concentrationconcentrated to dryness
  7. custompurified by preparatory TLC (EtOAc)

Sources & evidence

ORD record
ord-e9c93700b89c4ee9b95127e4b3497bfa
Source dataset
uspto-grants-2015_11
Patent number
US09181223B2

Reaction notes

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