Acetic Acid → Tert-butyl 4-(3-(3,5-dichlorophenylamino)-1H-1,2,4-triazol-5-ylamino)piperidine-1-carboxylate

HRID 1486592Notes

Reaction equation

HRID 1486592 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[N:14]=[C:13]([NH2:15])[NH:12][N:11]=2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.ClC1C=C(N=C=S)C=C(Cl)C=1C#N.O=[C:30]1[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]1.C(O)(=O)C>CO>[C:39]([O:38][C:36]([N:33]1[CH2:34][CH2:35][CH:30]([NH:15][C:13]2[NH:12][N:11]=[C:10]([NH:9][C:4]3[CH:5]=[C:6]([Cl:8])[CH:7]=[C:2]([Cl:1])[CH:3]=3)[N:14]=2)[CH2:31][CH2:32]1)=[O:37])([CH3:42])([CH3:40])[CH3:41]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 727146143-Amino-5-(3,5-dichloroanilino)-s-triazoleHCID 867076002,6-Dichloro-4-isothiocyanatobenzonitrile

Product 1

HCID 178452086Tert-butyl 4-(3-(3,5-dichlorophenylamino)-1H-1,2,4-triazol-5-ylamino)piperidine-1-carboxylateYield 88%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of N3-(3,5-dichlorophenyl)-1H-1,2,4-triazole-3,5-diamine Intermediate 2 (122 mg, 0.5 mmol) in 10 ml of methanol, tert-butyl 4-oxopiperidine-1-carboxylate (102 mg, 0.512 mmol), was added acetic acid (0.05 mL). The mixture was stirred at rt for 15 min, after which picolineborane (112 mg, 1.047 mmol) was added. The mixture was stirred at rt overnight. LCMS indicated 87% product and 13% SM. Additional picolineborane (50 mg, 0.467 mmol) was added and the mixture was stirred for an additional 24 hours. The solvent was removed under reduced pressure and the residue was dissolved in methylene chloride and treated with saturated sodium bicarbonate to pH=9. The organic layer was separated and the aqueous layer was extracted with methylene chloride (3×10 mL). The solvent was reduced to about 4 mL and the residue was loaded onto a silica gel column. Eluting with 5% methanol/methylene chloride gave 188 mg (88%) of desired product as white solid. MS +m/z: 427.0 (M+H)+

Workup

  1. additionafter which picolineborane (112 mg, 1.047 mmol) was added
  2. stirringThe mixture was stirred at rt overnight
  3. additionAdditional picolineborane (50 mg, 0.467 mmol) was added
  4. stirringthe mixture was stirred for an additional 24 hours
  5. customThe solvent was removed under reduced pressure
  6. dissolutionthe residue was dissolved in methylene chloride
  7. additiontreated with saturated sodium bicarbonate to pH=9
  8. customThe organic layer was separated
  9. extractionthe aqueous layer was extracted with methylene chloride (3×10 mL)
  10. washEluting with 5% methanol/methylene chloride

Sources & evidence

ORD record
ord-a26851db74834ced86f2e4f6eac1ead8
Source dataset
uspto-grants-2016_08
Patent number
US09428469B2

Reaction notes

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