Pivaloyl chloride → N-{2-tert-Butyl-1-[(4,4-difluorocyclohexyl)methyl]-1H-benzimidazol-5-yl}acetamide

HRID 1435489

반응식

HRID 1435489 반응식
[NH2:1][C:2]1[CH:3]=[C:4]([NH:18][C:19](=[O:21])[CH3:20])[CH:5]=[CH:6][C:7]=1[NH:8][CH2:9][CH:10]1[CH2:15][CH2:14][C:13]([F:17])([F:16])[CH2:12][CH2:11]1.[CH3:22][C:23]([CH3:28])([CH3:27])[C:24](Cl)=O>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:23]([C:28]1[N:8]([CH2:9][CH:10]2[CH2:15][CH2:14][C:13]([F:17])([F:16])[CH2:12][CH2:11]2)[C:7]2[CH:6]=[CH:5][C:4]([NH:18][C:19](=[O:21])[CH3:20])=[CH:3][C:2]=2[N:1]=1)([CH3:27])([CH3:24])[CH3:22]

참가 물질

5

반응물 2

HCID 62493Pivaloyl chlorideHCID 57441085N-(3-Amino-4-{[(4,4-difluorocyclohexyl)methyl]amino}phenyl)acetamide

생성물 1

HCID 57723211N-{2-tert-Butyl-1-[(4,4-difluorocyclohexyl)methyl]-1H-benzimidazol-5-yl}acetamide

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매

실험 절차

N-(3-Amino-4-{[(4,4-difluorocyclohexyl)methyl]amino}phenyl)acetamide (1.32 g, 4.44 mmol) was dissolved in 100 mL of DCM containing DMAP (108 mg, 0.89 mmol). Trimethylacetyl chloride (0.60 mL, 4.88 mmol) was added dropwise and the solution was stirred at rt for 2 h. The solution washed with saturated aqueous NaHCO3 solution, saturated aqueous NaCl solution and dried over anhydrous Na2SO4. Part of the product precipitated during the washings and was filtered. The organic phase was evaporated and combined with the precipitate. The product was dissolved in 30 mL of AcOH and placed in 6 sealed tubes (5 mL/tube). Each tube was heated at 150° C. in a Personal Chemistry microwaves instrument for 2.5 h. The fractions were pooled and the solvent was evaporated. The product was dissolved in EtOAc and washed with aqueous NaHCO3 solution, saturated aqueous NaCl solution and dried over anhydrous Na2SO4. The product was purified by flash chromatography on silica gel using acetone/hexanes (2:1) as eluent. Yield: 1.11 g (68%); 1H NMR (400 MHz, CD3OD) δ 1.40-1.49 (m, 2 H), 1.52 (s, 9 H), 1.60-1.65 (m, 2 H), 1.67-1.77 (m, 1 H), 1.96-2.06 (m, 3 H), 2.11 (s, 3 H), 2.15-2.23 (m, 1 H), 4.28 (d, J=7.62 Hz, 2 H), 7.35-7.39 (m, 1 H), 7.40-7.44 (m, 1 H), 7.85 (d, J=1.76 Hz, 1 H).

후처리

  1. washThe solution washed with saturated aqueous NaHCO3 solution, saturated aqueous NaCl solution
  2. dry with materialdried over anhydrous Na2SO4
  3. customPart of the product precipitated during the washings
  4. filtrationwas filtered
  5. customThe organic phase was evaporated
  6. dissolutionThe product was dissolved in 30 mL of AcOH
  7. temperatureEach tube was heated at 150° C. in a Personal Chemistry microwaves instrument for 2.5 h
  8. customthe solvent was evaporated
  9. dissolutionThe product was dissolved in EtOAc
  10. washwashed with aqueous NaHCO3 solution, saturated aqueous NaCl solution
  11. dry with materialdried over anhydrous Na2SO4
  12. customThe product was purified by flash chromatography on silica gel

출처 및 근거

ORD 기록
ord-e5c3934385034e5bb7ce8cc91e71d662
출처 데이터셋
uspto-grants-2009_11
특허 번호
US07615642B2

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