Water → HCID 118006473, compound

HRID 1484714Notes

Reaction equation

HRID 1484714 reaction equation
[H-].[Na+].[OH:3][CH:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:15]=[C:14]([CH3:16])[C:13]([C:17]3[N:18]=[C:19]([NH:22][C:23](=[O:30])[C:24]4[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=4)[S:20][CH:21]=3)=[C:12]([CH3:31])[CH:11]=2)[CH2:6][CH2:5]1.[N:32]([CH2:35][CH2:36][O:37][CH2:38][CH2:39][O:40][CH2:41][CH2:42][O:43][CH2:44][CH2:45]I)=[N+:33]=[N-:34].O>CN(C=O)C>[N:32]([CH2:35][CH2:36][O:37][CH2:38][CH2:39][O:40][CH2:41][CH2:42][O:43][CH2:44][CH2:45][O:3][CH:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:15]=[C:14]([CH3:16])[C:13]([C:17]3[N:18]=[C:19]([NH:22][C:23](=[O:30])[C:24]4[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=4)[S:20][CH:21]=3)=[C:12]([CH3:31])[CH:11]=2)[CH2:6][CH2:5]1)=[N+:33]=[N-:34]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 71551921HCID 71551921, compoundHCID 118005907HCID 118005907, compound

Product 1

HCID 118006473HCID 118006473, compoundYield 21.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
50 °C

Procedure

NaH (13.2 mg, 60% in mineral oil, 0.330 mmol) was added to a 0° C. solution of N-(4-(4-(4-hydroxypiperidin-1-yl)-2,6-dimethylphenyl)thiazol-2-yl)isonicotinamide (14.8 mg, 0.0362 mmol) in dry DMF (0.5 mL); the mixture was then stirred at 50° C. for 20 min. After that, the mixture was cooled to 0° C., and a solution of 1-azido-2-(2-(2-(2-iodoethoxyl)ethoxy)ethoxy)ethane (14.3 mg, 0.0435 mmol)6 in DMF (0.15 mL) was added dropwise. The mixture was stirred at rt overnight. Water (2 mL) was added to quench the reaction, and the mixture was extracted with DCM (4×2 mL). The combined organic layer was washed with brine and concentrated. The residue was briefly purified on a short silica column (EtOAc) to furnish N-(4-(4-(4-(2-(2-(2-(2-azidoethoxyl)ethoxy)ethoxy)ethoxy)piperidin-1-yl)-2,6-dimethylphenyl)thiazol-2-yl)isonicotinamide (4.7 mg, 21.3%). MS (ESI) m/z 632.4 (M+Na+).

Workup

  1. temperatureAfter that, the mixture was cooled to 0° C.
  2. stirringThe mixture was stirred at rt overnight
  3. customto quench
  4. customthe reaction
  5. extractionthe mixture was extracted with DCM (4×2 mL)
  6. washThe combined organic layer was washed with brine
  7. concentrationconcentrated
  8. customThe residue was briefly purified on a short silica column (EtOAc)

Sources & evidence

ORD record
ord-d526ebc94b8a435a883a847f4744ec24
Source dataset
uspto-grants-2016_08
Patent number
US09422275B2

Reaction notes

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