Lithium Hexamethyldisilazide → HCID 89525879, compound

HRID 571391Notes

Reaction equation

HRID 571391 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]2[CH:8]=[N:9][N:10]([C:11]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:4]=2[CH:3]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.C[Si]([N-:59][Si](C)(C)C)(C)C.[Li+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.C1COCC1>[C:11]([N:10]1[C:4]2[CH:3]=[C:2]([NH2:59])[N:7]=[CH:6][C:5]=2[CH:8]=[N:9]1)([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

7

Reactant 3

HCID 2733832Lithium Hexamethyldisilazide2×HCID 27342162-(Dicyclohexylphosphino)biphenylHCID 895260086-chloro-1-trityl-1H-pyrazolo[4,3-c]pyridine

Product 1

HCID 89525879HCID 89525879, compoundYield 84%

Reagents, catalysts & solvents 3

HCID 27342162-(Dicyclohexylphosphino)biphenylCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A microwave vial was charged with 6-chloro-1-trityl-1H-pyrazolo[4,3-c]pyridine (1.02 g, 2.58 mmol), Pd2(dba)3 (0.24 g, 0.262 mmol), 2-(dicyclohexylphosphino) biphenyl (0.1 g, 0.285 mmol) and THF (11 mL). The mixture was evacuated and purged with nitrogen 5 times. Lithium bis(trimethylsilyl)amide (4.0 ml, 4.0 mmol, 1M in THF) was added dropwise and the mixture was heated at 70° C. for 2 h. Pd2(dba)3 (0.12 g, 0.131 mmol), 2-(dicyclohexylphosphino) biphenyl (0.05 g, 0.142 mmol) and LiHMDS (2.0 ml, 2.0 mmol, 1M in THF) were added again. After 16 h, the mixture was quenched with saturated NH4Cl and extracted with 2-methyltetrahydrofuran. The organic phase was washed with water, brine, dried (Na2SO4) and concentrated in vacuo to afford a residue, which was purified by chromatography on silica gel (MeOH in DCM, 0-8% 15 CV, 8-10% 10 CV) to afford 1-trityl-1H-pyrazolo[4,3-c]pyridin-6-amine (0.813 g, 2.16 mmol, 84%). MS ESI calc'd. for C25H21N4 [M+H]+ 377, found 377.

Workup

  1. customThe mixture was evacuated
  2. custompurged with nitrogen 5 times
  3. customthe mixture was quenched with saturated NH4Cl
  4. extractionextracted with 2-methyltetrahydrofuran
  5. washThe organic phase was washed with water, brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customto afford a residue, which
  9. customwas purified by chromatography on silica gel (MeOH in DCM, 0-8% 15 CV, 8-10% 10 CV)

Sources & evidence

ORD record
ord-d3783f6c1b5d40c88f5dc49b6f7e11c8
Source dataset
uspto-grants-2015_05
Patent number
US09023865B2

Reaction notes

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