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 1092038

反応式

HRID 1092038 の反応式
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

参加物

5

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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+)

後処理

  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

出典と根拠

ORDレコード
ord-d85d9ab9a40649a29937a1080c45a006
出典データセット
uspto-grants-2012_03
特許番号
US08129391B2

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