Sodium Thiosulfate → HCID 86268245, compound

HRID 710007Notes

Reaction equation

HRID 710007 reaction equation
C[O:2][C:3]1[C:8]([C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]3[CH:21]=[CH:20][N:19]=[C:18]([C:22]4[CH:23]=[N:24][N:25]([CH3:27])[CH:26]=4)[CH:17]=3)=[C:11]([CH3:28])[N:10]=2)=[CH:7][N:6]=[C:5]([NH:29][CH:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)[N:4]=1.[Si](I)(C)(C)C.[O-]S([O-])(=S)=O.[Na+].[Na+].C1COCC1.CCOC(C)=O>ClCCCl>[CH3:28][C:11]1[N:10]=[C:9]([C:8]2[C:3](=[O:2])[NH:4][C:5]([NH:29][CH:30]3[CH2:31][CH2:32][O:33][CH2:34][CH2:35]3)=[N:6][CH:7]=2)[CH:14]=[CH:13][C:12]=1[O:15][C:16]1[CH:21]=[CH:20][N:19]=[C:18]([C:22]2[CH:23]=[N:24][N:25]([CH3:27])[CH:26]=2)[CH:17]=1

Participants

6

Reactant 4

HCID 24477Sodium ThiosulfateHCID 85247Trimethylsilyl iodideHCID 21939870Tetrahydrofuran ethyl acetateHCID 90417124HCID 90417124, compound

Product 1

HCID 86268245HCID 86268245, compoundYield 6.3%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 4-methoxy-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrimidin-2-amine (0.125 g, 0.264 mmol) in DCE (3 mL) was treated with TMS-I (1.078 mL, 7.92 mmol), heated at 60° C. for 5 h, then cooled to RT and stirred overnight. The mixture was treated with 10% Na2S2O3 and 1:1 THF/EtOAc, stirred for 0.5 h, the layers separated, the aqueous layer extracted with EtOAc (1×) and the combined organics were washed with brine, dried over MgSO4 and concentrated to dryness. The material was treated with MeCN, heated to near-reflux and allowed to stand at RT over the weekend. The solid was removed via filtration, the filtrate concentrated to dryness and purified via silica gel chromatography (MeOH/EtOAc). The resulting material was treated with 10% MeOH/DCM, filtered to remove solids and concentrated to dryness to afford 5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4(3H)-one (7.7 mg, 6%). 1H NMR (400 MHz, DMSO-d6): δ10.96 (br s, 1H), 8.67 (s, 1H), 8.35 (d, J=5.7 Hz, 1H), 8.29-8.24 (m, 2H), 7.96 (s, 1H), 7.51 (d, J=8.6 Hz, 1H), 7.22 (d, J=2.4 Hz, 1H), 7.00 (br s, 1H), 6.60 (dd, J=5.7, 2.4 Hz, 1H), 3.98 (m, 1H), 3.87-3.80 (m, 5H), 3.39 (m, 2H), 2.34 (s, 3H), 1.85 (m, 2H), 1.47 (m, 2H); MS (ESI) m/z: 460.2 (M+H+).

Workup

  1. temperaturecooled to RT
  2. stirringstirred for 0.5 h
  3. customthe layers separated
  4. extractionthe aqueous layer extracted with EtOAc (1×)
  5. washthe combined organics were washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated to dryness
  8. additionThe material was treated with MeCN
  9. temperatureheated
  10. temperatureto near-reflux
  11. customto stand at RT over the weekend
  12. customThe solid was removed via filtration
  13. concentrationthe filtrate concentrated to dryness
  14. custompurified via silica gel chromatography (MeOH/EtOAc)
  15. additionThe resulting material was treated with 10% MeOH/DCM
  16. filtrationfiltered
  17. customto remove solids
  18. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-3e7ed291b4df495faf07e7c37ec13cbb
Source dataset
uspto-grants-2015_11
Patent number
US09181223B2

Reaction notes

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