Hydrochloric Acid → HCID 178496512, 화합물

HRID 538409노트

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HRID 538409 반응식
[Br:1][C:2]1[N:3]=[C:4]([C:25]([CH3:28])([CH3:27])[CH3:26])[NH:5][C:6]=1[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH2:14][C@@H:15]([NH:17]C(=O)OC(C)(C)C)[CH3:16])[N:8]=1.Cl.C(N(C(C)C)CC)(C)C.[CH3:39][O:40][CH2:41][C:42](Cl)=[O:43]>CO.C(Cl)Cl>[Br:1][C:2]1[N:3]=[C:4]([C:25]([CH3:27])([CH3:28])[CH3:26])[NH:5][C:6]=1[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH2:14][C@@H:15]([NH:17][C:42](=[O:43])[CH2:41][O:40][CH3:39])[CH3:16])[N:8]=1

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 96623Methoxyacetyl chlorideHCID 178461767(S)-tert-butyl 1-(4-(4-bromo-2-tert-butyl-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate

생성물 1

HCID 178496512HCID 178496512, 화합물수율 69.5%

시약·촉매·용매 2

HCID 887Methanol용매HCID 6344Dichloromethane용매

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온도
60 °C

실험 절차

A solution of (S)-tert-butyl 1-(4-(4-bromo-2-tert-butyl-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate (2.6 g, 4.4 mmol) in methanol was treated with aqueous 12 N HCl (1.4 mL. 16.8 mmol). The reaction was heated at 60° C. for 1 h, and allowed to cool to rt. The reaction was then concentrated and dried in vacuo to give 1.6 g of a crude residue which was carried forward without further purification. The residue was treated with diisopropylethyl amine (4.6 mL, 26.3 mmol) in dry DCM (18 mL), followed by the dropwise addition of methoxyacetyl chloride (0.44 mL, 4.8 mmol). The reaction mixture was stirred at rt for 1 h, then concentrated, in vacuo, to dryness. The remaining residue was dissolved in EtOAc (40 mL) was washed with water (2×), dried (Na2SO4), and concentrated. The crude residue was purified by flash chromatography (SiO2, 90:10-50:50 hexanes-EtOAc) to afford 1.3 g of (S)—N-(1-(4-(4-bromo-2-tert-butyl-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-yl)-2-methoxyacetamide:

후처리

  1. temperatureto cool to rt
  2. concentrationThe reaction was then concentrated
  3. customdried in vacuo
  4. customto give 1.6 g of a crude residue which
  5. customwas carried forward without further purification
  6. concentrationconcentrated, in vacuo, to dryness
  7. dissolutionThe remaining residue was dissolved in EtOAc (40 mL)
  8. washwas washed with water (2×)
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated
  11. customThe crude residue was purified by flash chromatography (SiO2, 90:10-50:50 hexanes-EtOAc)

출처 및 근거

ORD 기록
ord-94baaa4a0af54ec1b7d164a80d2f2756
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08865732B2

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