5-Chloro-2-fluorobenzonitrile → 2-[(3-Benzyltriazol-4-yl)amino]-5-chloro-benzonitrile

HRID 1519134Notes

Reaction equation

HRID 1519134 reaction equation
[CH2:1]([N:8]1[C:12]([NH2:13])=[CH:11][N:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:14][C:15]1[CH:16]=[CH:17][C:18](F)=[C:19]([CH:22]=1)[C:20]#[N:21].[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[CH2:1]([N:8]1[C:12]([NH:13][C:18]2[CH:17]=[CH:16][C:15]([Cl:14])=[CH:22][C:19]=2[C:20]#[N:21])=[CH:11][N:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 936535-Chloro-2-fluorobenzonitrileHCID 2733832Lithium HexamethyldisilazideHCID 233617711-benzyl-1H-1,2,3-triazol-5-amine

Product 1

HCID 867240552-[(3-Benzyltriazol-4-yl)amino]-5-chloro-benzonitrileYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

1-Benzyl-1H-1,2,3-triazol-5-amine 5a (1.00 g, 5.74 mmol) and 5-chloro-2-fluoro-benzonitrile (892.9 mg, 5.74 mmol) were combined in THF (6 mL) and cooled to −78° C. LiHMDS (6.31 mL of 1 M, 6.31 mmol) was added dropwise and the reaction stirred for 5 min and then allowed to warm to room temperature and subsequently heated at 60° C. for 1 h. The mixture was quenched water and then evaporated and the residue partitioned between EtOAc and 1M HCl, the organic layer separated and concentrated. Trituration of the residue in EtOAc and hexanes afforded 2-[(3-benzyltriazol-4-yl)amino]-5-chloro-benzonitrile as a brown solid (1.06 g, 60%). MS m/z: 310.1 (M+H)+.

Workup

  1. temperatureto warm to room temperature
  2. temperaturesubsequently heated at 60° C. for 1 h
  3. customThe mixture was quenched water
  4. customevaporated
  5. customthe residue partitioned between EtOAc and 1M HCl
  6. customthe organic layer separated
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-bf5062cfdee74b6788c19c9efc0a1db4
Source dataset
uspto-grants-2015_07
Patent number
US09073875B2

Reaction notes

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