Sodium bis(trimethylsilyl)amide → N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-2-[(3-methyl-1,2-oxazol-5-yl)methylamino]benzamide

HRID 16768

Reaction equation

HRID 16768 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[NH2:11][C:12]1[N:16](C(OC(C)(C)C)=O)[N:15]=[C:14]([CH2:24][CH2:25][C:26]2[CH:31]=[C:30]([O:32][CH3:33])[CH:29]=[C:28]([O:34][CH3:35])[CH:27]=2)[CH:13]=1.[CH3:36][C:37]1[CH:41]=[C:40]([CH2:42][NH:43][C:44]2[CH:53]=[CH:52][CH:51]=[CH:50][C:45]=2[C:46](OC)=[O:47])[O:39][N:38]=1>C1COCC1>[CH3:33][O:32][C:30]1[CH:31]=[C:26]([CH2:25][CH2:24][C:14]2[NH:15][N:16]=[C:12]([NH:11][C:46](=[O:47])[C:45]3[CH:50]=[CH:51][CH:52]=[CH:53][C:44]=3[NH:43][CH2:42][C:40]3[O:39][N:38]=[C:37]([CH3:36])[CH:41]=3)[CH:13]=2)[CH:27]=[C:28]([O:34][CH3:35])[CH:29]=1

Participants

5

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 57440371Tert-butyl 5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]pyrazole-1-carboxylateHCID 57440405Methyl 2-{[(3-methylisoxazol-5-yl)methyl]amino}-benzoate

Product 1

HCID 66589749N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-2-[(3-methyl-1,2-oxazol-5-yl)methylamino]benzamideYield 10.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

NaHMDS (1M solution in THF, 0.83 ml, 0.828 mmol, 2.5 eq) was added dropwise to a solution of tert-butyl 5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazole-1-carboxylate (90 mg, 0.364 mmol, 1.1 eq) and methyl 2-{[(3-methylisoxazol-5-yl)methyl]amino}-benzoate (115 mg, 0.331 mmol, 1 eq), stirred in THF (4 ml) under nitrogen. The solution was stirred at room temperature for 50 mins. The solution was quenched with satd. aq. NH4Cl, diluted with water (5 ml) and extracted with ethyl acetate (3×8 ml). The crude product was purified by silica column chromatography, eluting with a gradient of 0-1.5% MeOH in DCM. Fractions containing product were evaporated and further purified by reverse phase prep. HPLC purification, eluting with a gradient of MeCN/H2O+0.1% TFA to afford the title compound as an off-white solid (16 mg, 10% yield); 1H NMR (399.902 MHz, DMSO) δ 2.20 (s, 3H), 2.88 (s, 4H), 3.73 (s, 6H), 4.57 (s, 2H), 6.21 (s, 1H), 6.33 (t, 1H), 6.41 (bs, 1H), 6.43 (d, 3H), 6.65 (t, 1H), 6.77 (d, 1H), 7.28-7.34 (m, 1H), 7.75-7.79 (m, 1H), 8.10 (bs, 1H), 10.50 (s, 1H). MS: m/z 462 (MH+)

Workup

  1. customThe solution was quenched with satd
  2. additionaq. NH4Cl, diluted with water (5 ml)
  3. extractionextracted with ethyl acetate (3×8 ml)
  4. customThe crude product was purified by silica column chromatography
  5. washeluting with a gradient of 0-1.5% MeOH in DCM
  6. additionFractions containing product
  7. customwere evaporated
  8. customfurther purified by reverse phase prep
  9. customHPLC purification
  10. washeluting with a gradient of MeCN/H2O+0.1% TFA

Sources & evidence

ORD record
ord-c2b0d3294757420a8f43a903470ee3c2
Source dataset
uspto-grants-2010_06
Patent number
US07737149B2

Linked notes

Loading…