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

HRID 1486297Notes

Reaction equation

HRID 1486297 reaction equation
[F:1][C:2]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:3]=1[CH2:4][O:5][C:6]1[N:11]2[N:12]=[C:13]([CH3:18])[C:14]([C:15]([OH:17])=O)=[C:10]2[CH:9]=[CH:8][CH:7]=1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[C:46]([O:50][C:51](=[O:60])[NH:52][C:53]([CH3:59])([CH2:56][CH2:57][CH3:58])[CH2:54][NH2:55])([CH3:49])([CH3:48])[CH3:47].C(N(CC)C(C)C)(C)C>O1CCCC1>[C:46]([O:50][C:51](=[O:60])[NH:52][C:53]([CH3:59])([CH2:56][CH2:57][CH3:58])[CH2:54][NH:55][C:15]([C:14]1[C:13]([CH3:18])=[N:12][N:11]2[C:6]([O:5][CH2:4][C:3]3[C:2]([F:1])=[CH:22][CH:21]=[CH:20][C:19]=3[F:23])=[CH:7][CH:8]=[CH:9][C:10]=12)=[O:17])([CH3:49])([CH3:48])[CH3:47]

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 1178595867-[(2,6-Difluorobenzyl)oxy]-2-methylpyrazolo[1,5-a]pyridine-3-carboxylic Acid

Product 1

HCID 121434576rac-{1-[({7-[(2,6-Difluorobenzyl)oxy]-2-methylpyrazolo[1,5-a]pyridin-3-yl}carbonyl)amino]-2-methylpentan-2-yl}carbamic Acid tert-butyl Ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 100 mg (0.19 mmol, 61% pure) of 7-[(2,6-difluorobenzyl)oxy]-2-methylpyrazolo[1,5-a]pyridine-3-carboxylic acid from Example 130A in 4 ml of tetrahydrofuran was admixed with 39.1 mg (0.287 mmol) of 1-hydroxybenzotriazole and 74.3 mg (0.287 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. The resulting solution was stirred at room temperature for 15 min, and then 62.2 mg (0.287 mmol) of rac-(1-amino-2-methylpentan-2-yl)carbamic acid tert-butyl ester from Example 152A were added, followed by 0.1 ml (0.575 mmol) of N,N-diisopropylethylamine After the addition, the mixture was stirred at room temperature for a further 15 h. The solvent was drawn off under reduced pressure and the residue was partitioned between dichloromethane (10 ml) and water (10 ml). The organic phase was removed and washed with water and saturated aqueous sodium chloride solution, dried with a phase separation cartridge and concentrated under reduced pressure, which gave 45 mg (24% of theory, 53% pure) of the target compound.

Workup

  1. additionAfter the addition
  2. stirringthe mixture was stirred at room temperature for a further 15 h
  3. customthe residue was partitioned between dichloromethane (10 ml) and water (10 ml)
  4. customThe organic phase was removed
  5. washwashed with water and saturated aqueous sodium chloride solution
  6. customdried with a phase separation cartridge
  7. concentrationconcentrated under reduced pressure, which
  8. customgave 45 mg (24% of theory, 53% pure) of the target compound

Sources & evidence

ORD record
ord-459c0a2febc7489791175589b636213e
Source dataset
uspto-grants-2016_08
Patent number
US09422285B2

Reaction notes

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