1-Hydroxybenzotriazole → rac-{1-[({7-[(2-Chloro-6-fluorobenzyl)oxy]-2,5-dimethylpyrazolo[1,5-a]pyridin-3-yl}carbonyl)amino]-2-methylpentan-2-yl}carbamic Acid tert-butyl Ester

HRID 1486304Notes

Reaction equation

HRID 1486304 reaction equation
[Cl:1][C:2]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:3]=1[CH2:4][O:5][C:6]1[N:11]2[N:12]=[C:13]([CH3:18])[C:14]([C:15](O)=[O:16])=[C:10]2[CH:9]=[C:8]([CH3:19])[CH:7]=1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[C:47]([O:51][C:52](=[O:61])[NH:53][C:54]([CH2:59][NH2:60])([CH3:58])[CH2:55][CH2:56][CH3:57])([CH3:50])([CH3:49])[CH3:48].C(N(CC)C(C)C)(C)C>O1CCCC1>[C:47]([O:51][C:52](=[O:61])[NH:53][C:54]([CH3:58])([CH2:55][CH2:56][CH3:57])[CH2:59][NH:60][C:15]([C:14]1[C:13]([CH3:18])=[N:12][N:11]2[C:6]([O:5][CH2:4][C:3]3[C:20]([F:24])=[CH:21][CH:22]=[CH:23][C:2]=3[Cl:1])=[CH:7][C:8]([CH3:19])=[CH:9][C:10]=12)=[O:16])([CH3:48])([CH3:49])[CH3:50]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 84723920rac-tert-Butyl (1-amino-2-methylpentan-2-yl)carbamateHCID 1178595577-(2-Chloro-6-fluorobenzyloxy)-2,5-dimethylpyrazolo[1,5-a]pyridine-3-carboxylic Acid

Product 1

HCID 117864595rac-{1-[({7-[(2-Chloro-6-fluorobenzyl)oxy]-2,5-dimethylpyrazolo[1,5-a]pyridin-3-yl}carbonyl)amino]-2-methylpentan-2-yl}carbamic Acid tert-butyl EsterYield 99%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 26 mg (0.074 mmol) of 7-(2-chloro-6-fluorobenzyloxy)-2,5-dimethylpyrazolo[1,5-a]pyridine-3-carboxylic acid (Example 137A) in 3 ml of tetrahydrofuran was admixed with 17 mg (0.09 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 14 mg (0.09 mmol) of 1-hydroxybenzotriazole, 21 mg (0.096 mmol) of rac-(1-aminomethyl-1-methylbutyl)carbamic acid tert-butyl ester from Example 152A and 0.039 ml (0.222 mmol) of N,N-diisopropylethylamine. The mixture was stirred at room temperature for a further 18 hours. The reaction mixture was then heated to 60° C. for 3 hours. After concentration under reduced pressure, the residue was partitioned between dichloromethane and water. The organic phase was removed and concentrated under reduced pressure, which gave 40 mg (99% yield) of the target compound.

Workup

  1. temperatureThe reaction mixture was then heated to 60° C. for 3 hours
  2. concentrationAfter concentration under reduced pressure
  3. customthe residue was partitioned between dichloromethane and water
  4. customThe organic phase was removed
  5. concentrationconcentrated under reduced pressure, which

Sources & evidence

ORD record
ord-c8c2640b235d41d3841a2223a691b67e
Source dataset
uspto-grants-2016_08
Patent number
US09422285B2

Reaction notes

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