Triethylamine → (2E)-3-[4-amino-2-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-7-yl]-N,N-dimethylprop-2-enamide

HRID 244881

반응식

HRID 244881 반응식
Br[C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:15]([CH2:16][CH:17]4[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)[C:14]([CH2:23][CH3:24])=[N:13][C:7]=3[C:8]([NH2:12])=[N:9][C:10]=2[CH:11]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C.[CH3:54][N:55]([CH3:60])[C:56](=[O:59])[CH:57]=[CH2:58]>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:12][C:8]1[C:7]2[N:13]=[C:14]([CH2:23][CH3:24])[N:15]([CH2:16][CH:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)[C:6]=2[C:5]2[CH:4]=[CH:3][C:2](/[CH:58]=[CH:57]/[C:56]([N:55]([CH3:60])[CH3:54])=[O:59])=[CH:11][C:10]=2[N:9]=1

참가 물질

7

반응물 4

HCID 8471TriethylamineHCID 17587N,N-DimethylacrylamideHCID 80271Tri-o-tolylphosphineHCID 690807877-bromo-2-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-4-amine

생성물 1

HCID 57657266(2E)-3-[4-amino-2-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-7-yl]-N,N-dimethylprop-2-enamide수율 63.8%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 6228Dimethylformamide용매3회

반응 조건

온도
120 °C

실험 절차

A thick walled glass vessel, equipped with a stir bar, was charged with a warmed solution of 7-bromo-2-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-4-amine (0.58 g, 1.5 mmol) in N,N-dimethylformamide (10 mL). To the solution was added in succession, a solution of palladium acetate (37 mg, 0.15 mmol) and tri-ortho-tolylphosphine (91 mg, 0.3 mmol) in N,N-dimethylformamide (5 mL), triethylamine (3.0 eq. 0.6 mL), and a solution of N,N-dimethylacrylamide (178 mg, 1.8 mmol) in N,N-dimethylformamide (2 mL). The reaction mixture was purged with nitrogen. The vessel was sealed and heated at 120° C. for 18 hours. The reaction was cooled to ambient temperature and then concentrated to dryness under reduced pressure. The resulting solid was dissolved in dichloromethane (100 mL) and washed with saturated aqueous potassium carbonate (50 mL). The fractions were separated and the organic fraction was concentrated to dryness. The resulting off-white solid was purified by chromatography using a HORIZON HPFC system, (silica cartridge, 0-15% CMA/chloroform). A final recrystallization from acetonitrile provided 390 mg of (2E)-3-[4-amino-2-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-7-yl]-N,N-dimethylprop-2-enamide as an off-white crystalline solid, mp>260° C.

후처리

  1. customA thick walled glass vessel, equipped with a stir bar
  2. additionTo the solution was added in succession
  3. customThe reaction mixture was purged with nitrogen
  4. customThe vessel was sealed
  5. temperatureThe reaction was cooled to ambient temperature
  6. concentrationconcentrated to dryness under reduced pressure
  7. dissolutionThe resulting solid was dissolved in dichloromethane (100 mL)
  8. washwashed with saturated aqueous potassium carbonate (50 mL)
  9. customThe fractions were separated
  10. concentrationthe organic fraction was concentrated to dryness
  11. customThe resulting off-white solid was purified by chromatography
  12. customA final recrystallization from acetonitrile

출처 및 근거

ORD 기록
ord-19a8b4a415304423bbbf1ac1baa5575b
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658666B2

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