Diisopropylethylamine → rac-{1-[({5-Cyclopropyl-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 1486315Notes

Reaction equation

HRID 1486315 reaction equation
ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH:23]1([C:26]2[CH:31]=[C:30]([O:32][CH2:33][C:34]3[C:39]([F:40])=[CH:38][CH:37]=[CH:36][C:35]=3[F:41])[N:29]3[N:42]=[C:43]([CH3:48])[C:44]([C:45](O)=[O:46])=[C:28]3[CH:27]=2)[CH2:25][CH2:24]1.C(N(CC)C(C)C)(C)C.[C:58]([O:62][C:63](=[O:72])[NH:64][C:65]([CH3:71])([CH2:68][CH2:69][CH3:70])[CH2:66][NH2:67])([CH3:61])([CH3:60])[CH3:59]>O1CCCC1>[C:58]([O:62][C:63](=[O:72])[NH:64][C:65]([CH3:71])([CH2:68][CH2:69][CH3:70])[CH2:66][NH:67][C:45]([C:44]1[C:43]([CH3:48])=[N:42][N:29]2[C:30]([O:32][CH2:33][C:34]3[C:35]([F:41])=[CH:36][CH:37]=[CH:38][C:39]=3[F:40])=[CH:31][C:26]([CH:23]3[CH2:25][CH2:24]3)=[CH:27][C:28]=12)=[O:46])([CH3:61])([CH3:60])[CH3:59]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 84723920rac-tert-Butyl (1-amino-2-methylpentan-2-yl)carbamateHCID 1178596065-Cyclopropyl-7-[(2,6-difluorobenzyl)oxy]-2-methylpyrazolo[1,5-a]pyridine-3-carboxylic Acid

Product 1

HCID 117864545rac-{1-[({5-Cyclopropyl-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

76 mg (0.6 mmol) of 1-hydroxy-7-azabenzotriazole and 107 mg (0.6 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were added to a solution of 167 mg (0.5 mmol) of 5-cyclopropyl-7-[(2,6-difluorobenzyl)oxy]-2-methylpyrazolo[1,5-a]pyridine-3-carboxylic acid (Example 149A), 244 μl (1.4 mmol) of N,N-diisopropylethylamine and 121 mg (0.6 mmol) of rac-(1-amino-2-methylpentan-2-yl)carbamic acid tert-butyl ester from Example 152A in 5 ml of tetrahydrofuran. The mixture was stirred at room temperature for 18 h and concentrated under reduced pressure. The residue was partitioned between ethyl acetate and water. The organic phase was removed and washed with water and saturated aqueous sodium chloride solution, dried over sodium sulphate, filtered and concentrated. The residue was purified by chromatography on silica gel (40 g silica gel cartridge, mobile phase: cyclohexane/ethyl acetate, gradient 0% to 100%). This gave 125 mg of the target compound (48% of theory).

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe residue was partitioned between ethyl acetate and water
  3. customThe organic phase was removed
  4. washwashed with water and saturated aqueous sodium chloride solution
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by chromatography on silica gel (40 g silica gel cartridge, mobile phase: cyclohexane/ethyl acetate, gradient 0% to 100%)

Sources & evidence

ORD record
ord-ce52306062f0473eb0dd8b0a47d35e5b
Source dataset
uspto-grants-2016_08
Patent number
US09422285B2

Reaction notes

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