Lithium Hexamethyldisilazide → HCID 86617877, compound

HRID 2426809Notes

Reaction equation

HRID 2426809 reaction equation
[C:1]([C:4]1[CH:9]=[C:8]([N:10]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:11][CH:12]2[CH2:14][CH:13]2[CH3:15])[N:7]=[C:6]([N:23]([CH3:30])[S:24]([CH:27]([CH3:29])[CH3:28])(=[O:26])=[O:25])[CH:5]=1)(=[O:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH2:41]([C@:48]([NH:52][C:53](=[O:59])[O:54][C:55]([CH3:58])([CH3:57])[CH3:56])([CH3:51])[CH:49]=O)[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1>C1COCC1>[CH2:41]([C@:48]([NH:52][C:53](=[O:59])[O:54][C:55]([CH3:58])([CH3:57])[CH3:56])([CH3:51])/[CH:49]=[CH:2]/[C:1]([C:4]1[CH:5]=[C:6]([N:23]([S:24]([CH:27]([CH3:29])[CH3:28])(=[O:25])=[O:26])[CH3:30])[N:7]=[C:8]([N:10]([CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:11][CH:12]2[CH2:14][CH:13]2[CH3:15])[CH:9]=1)=[O:3])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 58990158HCID 58990158, compound2×HCID 67252266HCID 67252266, compound

Product 1

HCID 86617877HCID 86617877, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a −78° C. solution of N-(4-acetyl-6-{benzyl[(2-methylcyclopropyl)methyl]amino}pyridin-2-yl)-N-methylpropane-2-sulfonamide (100 mg, 0.23 mmol) from Step B in 1.5 mL dry THF was added lithium bis(trimethylsilyl)amide (244 μL, 0.49 mmol, 2M solution in THF), and the resulting mixture was allowed to stir for 15 min. To this mixture was added a solution of tert-butyl (1R) -1-benzyl-1-methyl-2-oxoethylcarbamate (61 mg, 0.23 mmol, prepared according to preparation of intermediate III up to step C) dissolved in 1 mL dry THF. The solution was allowed to slowly warm to rt and then allowed to stir for an additional 16 h, at which time it was quenched with a saturated solution of ammonium chloride (15 mL) and extracted with ethyl acetate (2×25 mL). The combined organics were dried over sodium sulfate and concentrated. Purification by reverse-phase chromatography afforded tert-butyl (1R,2E)-1-benzyl-4-{2-{benzyl[(2-methylcyclopropyl)methyl]amino}-6-[(isopropylsulfonyl)(methyl)amino]pyridin-4-yl}-1-methyl-4-oxobut-2-enylcarbamate, intermediate n, as an orange oil. LCMS [M+H]=675.3.

Workup

  1. stirringto stir for an additional 16 h, at which time it
  2. customwas quenched with a saturated solution of ammonium chloride (15 mL)
  3. extractionextracted with ethyl acetate (2×25 mL)
  4. dry with materialThe combined organics were dried over sodium sulfate
  5. concentrationconcentrated
  6. customPurification by reverse-phase chromatography

Sources & evidence

ORD record
ord-2a1b556deca94a839a6f11ec77009134
Source dataset
uspto-grants-2011_06
Patent number
US07968571B2

Reaction notes

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