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

HRID 1486285Notes

Reaction equation

HRID 1486285 reaction equation
[F:1][C:2]1[C:23]([F:24])=[CH:22][CH:21]=[CH:20][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]=[C:8]([CH3:19])[CH:7]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.ON1C2C=CC=CC=2N=N1.[C:47]([O:51][C:52](=[O:61])[NH:53][C:54]([CH3:60])([CH2:57][CH2:58][CH3:59])[CH2:55][NH2:56])([CH3:50])([CH3:49])[CH3:48].C(N(CC)C(C)C)(C)C>CN(C=O)C>[C:47]([O:51][C:52](=[O:61])[NH:53][C:54]([CH3:60])([CH2:57][CH2:58][CH3:59])[CH2:55][NH:56][C:15]([C:14]1[C:13]([CH3:18])=[N:12][N:11]2[C:6]([O:5][CH2:4][C:3]3[CH:20]=[CH:21][CH:22]=[C:23]([F:24])[C:2]=3[F:1])=[CH:7][C:8]([CH3:19])=[CH:9][C:10]=12)=[O:17])([CH3:50])([CH3:49])[CH3:48]

Participants

7

Reactant 5

HCID 682631,1'-CarbonyldiimidazoleHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 84723920rac-tert-Butyl (1-amino-2-methylpentan-2-yl)carbamateHCID 1178597477-[(2,3-Difluorobenzyl)oxy]-2,5-dimethylpyrazolo[1,5-a]pyridine-3-carboxylic Acid

Product 1

HCID 117864617rac-{1-[({7-[(2,3-Difluorobenzyl)oxy]-2,5-dimethylpyrazolo[1,5-a]pyridin-3-yl}carbonyl)amino]-2-methylpentan-2-yl}carbamic Acid tert-butyl Ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 120 mg (0.336 mmol) of 7-[(2,3-difluorobenzyl)oxy]-2,5-dimethylpyrazolo[1,5-a]pyridine-3-carboxylic acid from Example 117A in 2 ml of DMF was admixed with 70.8 mg (0.437 mmol) of 1,1′-carbonyldiimidazole and 36 mg (0.235 mmol) of 1-hydroxybenzotriazole. After stirring at room temperature for 15 min, 94.4 mg (0.437 mmol) of rac-(1-amino-2-methylpentan-2-yl)carbamic acid tert-butyl ester from Example 152A were added, followed by 0.117 ml (0.672 mmol) of N,N-diisopropylethylamine. The tubes were sealed and introduced into a Biotage Initiator with microwave irradiation at 100° C. for 20 minutes. The reaction mixture was partitioned between ethyl acetate (10 ml) and water (10 ml), the phases were separated and the aqueous phase was acidified to pH=5 with 2 N aqueous hydrochloric acid and extracted with dichloromethane (2×15 ml). The combined organic phases were concentrated under reduced pressure and the residue was purified by flash chromatography using a prepacked silica gel cartridge (eluent:cyclohexane-ethyl acetate 10:1 to 1:1), which gave 35 mg (15% of theory, 78% pure) of the target compound.

Workup

  1. customThe tubes were sealed
  2. additionintroduced into a Biotage Initiator with microwave irradiation at 100° C. for 20 minutes
  3. customThe reaction mixture was partitioned between ethyl acetate (10 ml) and water (10 ml)
  4. customthe phases were separated
  5. extractionextracted with dichloromethane (2×15 ml)
  6. concentrationThe combined organic phases were concentrated under reduced pressure
  7. customthe residue was purified by flash chromatography
  8. customgave 35 mg (15% of theory, 78% pure) of the target compound

Sources & evidence

ORD record
ord-790d591272dd4b9881a1e59bb6a9e366
Source dataset
uspto-grants-2016_08
Patent number
US09422285B2

Reaction notes

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