Sodium bis(trimethylsilyl)amide → HCID 51357858, compound

HRID 1879377Notes

Reaction equation

HRID 1879377 reaction equation
[N:1]([C@@H:4]1[C:14]2[C:9](=[N:10][CH:11]=[CH:12][CH:13]=2)[C@H:8]([OH:15])[CH2:7][CH2:6][C@H:5]1[C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[C:18]([F:23])[CH:17]=1)=[N+]=[N-].[O:24]=[C:25]1[NH:33][C:28]2=[N:29][CH:30]=[CH:31][CH:32]=[C:27]2[N:26]1[CH:34]1[CH2:39][CH2:38][N:37]([C:40](OC2C=CC([N+]([O-])=O)=CC=2)=[O:41])[CH2:36][CH2:35]1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>CN(C)C=O>[O:24]=[C:25]1[NH:33][C:28]2=[N:29][CH:30]=[CH:31][CH:32]=[C:27]2[N:26]1[CH:34]1[CH2:35][CH2:36][N:37]([C:40]([O:15][C@H:8]2[C:9]3=[N:10][CH:11]=[CH:12][CH:13]=[C:14]3[C@@H:4]([NH2:1])[C@H:5]([C:16]3[CH:21]=[C:20]([F:22])[CH:19]=[C:18]([F:23])[CH:17]=3)[CH2:6][CH2:7]2)=[O:41])[CH2:38][CH2:39]1

Participants

5

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 579114044-nitrophenyl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxylateHCID 86658450HCID 86658450, compound

Product 1

HCID 51357858HCID 51357858, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a 100 mL round-bottom flask was suspended (5S,6S,9R)-5-azido-6-(3,5-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ol (46 mg, 0.145 mmol) (azeotroped with dry benzene) and 4-nitrophenyl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxylate (66.9 mg, 0.175 mmol) in dimethylformamide (1 mL) under nitrogen. After cooling to −15° C. (ice-methanol bath), NaHMDS (0.393 mL, 0.393 mmol) was added dropwise. The resulting tan solution was stirred under nitrogen at −10° C.˜0° C. for 2 h and at room temperature for 2 h. LCMS showed good conversion. The reaction was quenched with sodium bicarbonate solution. The mixture was diluted with ethyl acetate. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with water, brine, dried with sodium sulfate, and concentrated to give a tan oil. Purification by FCC up to 8% methanol/methylene chloride afforded the desired product (62 mg, 76%) as a white solid.

Workup

  1. customIn a 100 mL round-bottom flask was suspended
  2. additionwas added dropwise
  3. customThe reaction was quenched with sodium bicarbonate solution
  4. additionThe mixture was diluted with ethyl acetate
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with ethyl acetate
  7. washThe combined organic layers were washed with water, brine
  8. dry with materialdried with sodium sulfate
  9. concentrationconcentrated
  10. customto give a tan oil
  11. customPurification by FCC up to 8% methanol/methylene chloride

Sources & evidence

ORD record
ord-68b4ca86b4924538bb8aa03ceae92144
Source dataset
uspto-grants-2012_11
Patent number
US08314117B2

Reaction notes

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