Lithium Hexamethyldisilazide → HCID 178522169, compound

HRID 1875838Notes

Reaction equation

HRID 1875838 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:9]2[N:13]([CH2:14][CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]3)[C:12]3[CH:21]=[C:22]([F:26])[C:23]([F:25])=[CH:24][C:11]=3[N:10]=2)=[C:6]([NH2:8])[CH:7]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C[O:38][C:39](=O)[C:40]1[CH:45]=[CH:44][C:43]([C:46]2[NH:50][N:49]=[N:48][N:47]=2)=[CH:42][C:41]=1[F:51]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:9]2[N:13]([CH2:14][CH:15]3[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]3)[C:12]3[CH:21]=[C:22]([F:26])[C:23]([F:25])=[CH:24][C:11]=3[N:10]=2)=[C:6]([NH:8][C:39](=[O:38])[C:40]2[CH:45]=[CH:44][C:43]([C:46]3[NH:50][N:49]=[N:48][N:47]=3)=[CH:42][C:41]=2[F:51])[CH:7]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 67049939HCID 67049939, compoundHCID 178497604HCID 178497604, compound

Product 1

HCID 178522169HCID 178522169, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 5-chloro-2-(1-cyclohexylmethyl-5,6-difluoro-1H-benzoimidazol-2-yl)-phenylamine (60 mg, 0.16 mmol) in dry tetrahydrofuran (15 ml) was added lithium bis(trimethylsilyl)amide at −30° C. and stirring continued for 30 minutes at that temperature. To this was added a solution of 2-fluoro-4-(1H-tetrazol-5-yl)-benzoic acid methyl ester (42 mg, 0.19 mmol) in tetrahydrofuran (5 ml) at −30° C. The temperature was then allowed to slowly rise to 25° C., and the reaction mixture was allowed to stir for 13 h. The reaction mixture was quenched with saturated aqueous solution of ammonium chloride, extracted with ethyl acetate (3×5 ml). Combined organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography over silica gel (ethyl acetate to 4% methanol/ethyl acetate) gave the desired final compound as light yellow powder (30%). MS (Turbo Spray): m/z=566.4 (M+H).

Workup

  1. customto slowly rise to 25° C.
  2. stirringto stir for 13 h
  3. customThe reaction mixture was quenched with saturated aqueous solution of ammonium chloride
  4. extractionextracted with ethyl acetate (3×5 ml)
  5. washCombined organic layer was washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified by column chromatography over silica gel (ethyl acetate to 4% methanol/ethyl acetate)

Sources & evidence

ORD record
ord-61e036da85e34782bee7ff34fd122f33
Source dataset
uspto-grants-2012_11
Patent number
US08309581B2

Reaction notes

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