Imidazole → HCID 89918442, compound

HRID 921758Notes

Reaction equation

HRID 921758 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C@H:12]([OH:14])[CH3:13])[N:6]=[C:5]2[C:15]#[N:16].N1C=CN=C1.[Si:22](Cl)([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C@H:12]([O:14][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[CH3:13])[N:6]=[C:5]2[C:15]#[N:16]

Participants

6

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 86708639HCID 86708639, compound

Product 1

HCID 89918442HCID 89918442, compoundYield 83.8%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

(R)-5-amino-1-(2-hydroxypropyl)-1H-indazole-3-carbonitrile (180 mg, 0.832 mmol) was taken up in DCM (6 mL) and imidazole (227 mg, 3.33 mmol) and DMAP (10.17 mg, 0.083 mmol) were added, followed by TBS-Cl (439 mg, 2.91 mmol). The reaction was stirred at room temperature overnight. The reaction mixture was quenched with saturated NH4Cl solution and diluted with DCM. The organic layer was collected and washed with brine, dried over Na2SO4, filtered, and concentrated. The crude material was purified by flash column chromatography eluting with 0-40% EtOAc/Hex. (R)-5-amino-1-(2-((tert-butyldimethylsilyl)oxy)propyl)-1H-indazole-3-carbonitrile (230.5 mg) was obtained as an orange solid.

Workup

  1. customThe reaction mixture was quenched with saturated NH4Cl solution
  2. additiondiluted with DCM
  3. customThe organic layer was collected
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was purified by flash column chromatography
  9. washeluting with 0-40% EtOAc/Hex

Sources & evidence

ORD record
ord-cdc68dd09c5e4b0da54baf68a9b6012a
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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