Triethylamine → (S)-N-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-2-phenylpropanamide

HRID 548008

Reaction equation

HRID 548008 reaction equation
Cl.[CH3:2][C:3]1[C:7]([CH2:8][N:9]2[CH:13]=[C:12]([NH2:14])[CH:11]=[N:10]2)=[C:6]([CH3:15])[O:5][N:4]=1.[C:16]1([C@H:22]([CH3:26])[C:23](O)=[O:24])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>C(OCC)(=O)C.CN(C=O)C>[CH3:2][C:3]1[C:7]([CH2:8][N:9]2[CH:13]=[C:12]([NH:14][C:23](=[O:24])[C@H:22]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH3:26])[CH:11]=[N:10]2)=[C:6]([CH3:15])[O:5][N:4]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 27246222-Phenylpropionic acid, (+)-HCID 2724699PyBOPHCID 574222641-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-amine hydrochloride

Product 1

HCID 57944946(S)-N-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-2-phenylpropanamideYield 61.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-amine hydrochloride (Example 4-1a) (200 mg, 1 mmol), (S)-2-phenyl propionic acid (156 mg, 1 mmol), and PyBop (650 mg, 1.3 mmol) were added to DMF (4 mL) followed by triethylamine (0.3 mL, 2.1 mmol). The reaction stirred for 4 hours at room temperature under a nitrogen atmosphere then diluted with ethyl acetate (20 mL), washed with aqueous saturated NaHCO3 solution (2×15 mL) followed by aqueous saturated NaCl solution (15 mL). The organic phase was dried, filtered and concentrated on the rotovap. The crude product was re-suspended in methanol (3 mL) and purified by reversed phase HPLC (5%-95% ACN in H2O:25 minute gradient). The fractions containing the pure product were concentrated to afford (S)-N-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-2-phenylpropanamide (200 mg, 60%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 1.36 (d, J=7.2, Hz, 3H), 2.09 (s, 3H), 2.36 (s, 3H), 3.71-3.66 (m, 1H), 5.05 (s, 2H), 7.33-7.17 (m, 5H), 7.37 (s, 1H), 7.90 (s, 1H), 10.05 (s, 1H). MS 325 (M+H). Melting point 108° C.-110° C.

Workup

  1. washwashed with aqueous saturated NaHCO3 solution (2×15 mL)
  2. customThe organic phase was dried
  3. filtrationfiltered
  4. concentrationconcentrated on the rotovap
  5. custompurified by reversed phase HPLC (5%-95% ACN in H2O:25 minute gradient)
  6. additionThe fractions containing the pure product
  7. concentrationwere concentrated

Sources & evidence

ORD record
ord-8167fcbb4fb244dd859c2fa60b31e4be
Source dataset
uspto-grants-2011_05
Patent number
US07939671B2

Linked notes

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