Lithium Hexamethyldisilazide → HCID 178461496, compound

HRID 1835949Notes

Reaction equation

HRID 1835949 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[N:11]1[C:19]2[C:14](=[N:15][CH:16]=[CH:17][CH:18]=2)[NH:13][C:12]=1[CH2:20][C:21]([O:23]CC)=O.[NH2:26][C:27]1[CH:34]=[CH:33][CH:32]=[C:31]([N:35]2[CH2:40][C@H:39]([CH3:41])[O:38][C@H:37]([CH3:42])[CH2:36]2)[C:28]=1[C:29]#[N:30]>C1COCC1>[NH2:30][C:29]1[C:28]2[C:27](=[CH:34][CH:33]=[CH:32][C:31]=2[N:35]2[CH2:36][C@H:37]([CH3:42])[O:38][C@H:39]([CH3:41])[CH2:40]2)[NH:26][C:21](=[O:23])[C:20]=1[C:12]1[NH:13][C:14]2=[N:15][CH:16]=[CH:17][CH:18]=[C:19]2[N:11]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 686684862-amino-6-[(2R,6S)-2,6-dimethylmorpholin-4-yl]benzonitrileHCID 178470772HCID 178470772, compound

Product 1

HCID 178461496HCID 178461496, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

LiHMDS (3.0 eq) was added to ethyl 3H-imidazo[4,5-b]pyridin-2-ylacetate (1.0 eq) in THF at −78° C. After 20 minutes, a solution of 2-amino-6-[(2R,6S)-2,6-dimethylmorpholin-4-yl]benzonitrile (1.1 eq) in THF was added. The resulting mixture was allowed to warm to room temperature, stirred for 2 hours and then heated to 60° C. overnight. The mixture was cooled to 0° C. and quenched with an aqueous saturated NH4Cl solution. The aqueous phase was extracted with CH2Cl2 (5 times) and the organic extracts were collected, dried (Na2SO4), and concentrated. The crude product was purified by HPLC. LC/MS m/z 391.2 (MH+), Rt 2.35 minutes.

Workup

  1. temperatureheated to 60° C. overnight
  2. temperatureThe mixture was cooled to 0° C.
  3. customquenched with an aqueous saturated NH4Cl solution
  4. extractionThe aqueous phase was extracted with CH2Cl2 (5 times)
  5. customthe organic extracts were collected
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customThe crude product was purified by HPLC

Sources & evidence

ORD record
ord-a03df5589fea4b3e86e7f479db920153
Source dataset
uspto-grants-2004_08
Patent number
US06774237B2

Reaction notes

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