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 1911338

반응식

HRID 1911338 반응식
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

참가 물질

5

반응물 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

생성물 1

HCID 66589749N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-2-[(3-methyl-1,2-oxazol-5-yl)methylamino]benzamide수율 10,505.6%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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, 0.33 μmol, 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+)

후처리

  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

출처 및 근거

ORD 기록
ord-115ea4e837bf4b49b99a7fbdc24b61be
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08604022B2

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