Trimethylsilyl iodide → HCID 178430687, compound

HRID 869932Notes

Reaction equation

HRID 869932 reaction equation
[F:1][C:2]1([F:33])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:16][C:17]4[N:22]=[C:21]([C:23]5[C:24]([O:30]C)=[N:25][CH:26]=[C:27]([CH3:29])[CH:28]=5)[C:20]([CH3:32])=[CH:19][CH:18]=4)=[O:15])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1.[Si](I)(C)(C)C>CC#N.C(Cl)Cl.CCOC(C)=O>[F:33][C:2]1([F:1])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:16][C:17]4[N:22]=[C:21]([C:23]5[C:24]([OH:30])=[N:25][CH:26]=[C:27]([CH3:29])[CH:28]=5)[C:20]([CH3:32])=[CH:19][CH:18]=4)=[O:15])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1

Participants

5

Reactant 2

HCID 85247Trimethylsilyl iodideHCID 25118020HCID 25118020, compound

Product 1

HCID 178430687HCID 178430687, compoundYield 673.6%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 21226138Dichloromethane ethylacetateSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(2′-methoxy-3,5′-dimethyl-2,3′-bipyridin-6-yl)cyclopropanecarboxamide (0.181 g, 0.05 mmol) in CH3CN (0.5 mL) was added TMSI (114, 0.80 mmol) drop wise at 0° C. The reaction was stirred at 50° C. for 3 hours. The reaction was partitioned between ethyl acetate and H2O and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine and dried over MgSO4. After the removal of solvent, the residue was purified by column chromatography (0-10% MeOH-EtOAc) to yield a yellow solid. The solid was re-dissolved in DCM-EtOAc, washed with NaHSO3 (2×), brine, dried over MgSO4 and evaporated to dryness to yield 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(2′-hydroxy-3,5′-dimethyl-2,3′-bipyridin-6-yl)cyclopropanecarboxamide as a white solid (0.148 g, 84%). ESI-MS m/z calc. 439.41. found 440.2 (M+1)+. Retention time 1.51 minutes.

Workup

  1. customThe reaction was partitioned between ethyl acetate and H2O
  2. extractionthe aqueous layer was extracted with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. customAfter the removal of solvent
  6. customthe residue was purified by column chromatography (0-10% MeOH-EtOAc)
  7. customto yield a yellow solid
  8. washwashed with NaHSO3 (2×), brine
  9. dry with materialdried over MgSO4
  10. customevaporated to dryness

Sources & evidence

ORD record
ord-09b854081a464cf4891b88b58c577f27
Source dataset
uspto-grants-2015_03
Patent number
US08969386B2

Reaction notes

Loading…