Propylamine → 1-[4-amino-7-(1,3-dioxolan-2-ylmethoxy)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol

HRID 2203621노트

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HRID 2203621 반응식
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:13]=[CH:14][CH:15]=1)[NH2:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:16][CH2:17][C:18]([CH3:21])([OH:20])[CH3:19].[CH3:22][O:23][CH2:24][CH2:25][C:26](Cl)=O.C(OC1C=[CH:42][C:40]([NH2:41])=[CH:39]C=1)C1C=CC=CC=1.C(N)CC.C([O:50][CH2:51][C:52](Cl)=[O:53])C.C(OC1C=CC2[C:67]3[N:75](CC(C)(O)C)C(CCOC)=[N:73][C:68]=3[CH:69]=NC=2C=1)C1C=CC=CC=1.NC1C2N=C(CCOC)N(CC(O)(C)C)C=2C2C=CC(O)=CC=2N=1.BrCC1OCCO1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:15]=[CH:14][C:13]2[C:39]3[N:16]([CH2:17][C:18]([CH3:21])([OH:20])[CH3:19])[C:26]([CH2:25][CH2:24][O:23][CH3:22])=[N:41][C:40]=3[CH:42]=[N:12][C:11]=2[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1.[NH2:75][C:67]1[C:68]2[N:73]=[C:26]([CH2:25][CH2:24][O:23][CH3:22])[N:16]([CH2:17][C:18]([CH3:21])([OH:20])[CH3:19])[C:69]=2[C:13]2[CH:14]=[CH:15][C:9]([O:8][CH2:1][CH:2]3[O:50][CH2:51][CH2:52][O:53]3)=[CH:10][C:11]=2[N:12]=1

참가 물질

13

반응물 10

HCID 7852PropylamineHCID 11430Potassium Carbonate2회HCID 228604-BenzyloxyanilineHCID 780681,3-Dioxolane, 2-(bromomethyl)-2회HCID 84189Ethoxyacetyl chlorideHCID 928923-BenzyloxyanilineHCID 951022-Propanol, 1-amino-2-methyl-HCID 27597283-Methoxypropanoyl chlorideHCID 67051129[7-Benzyloxy-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-olHCID 1360752004-amino-1-(2-hydroxy-2-methylpropyl)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-7-ol2회

생성물 2

HCID 588336171-[4-amino-7-(1,3-dioxolan-2-ylmethoxy)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-olHCID 67051129[7-Benzyloxy-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
70 °C

실험 절차

[7-Benzyloxy-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol was prepared according to a modification of the methods described in Parts A-H of Example 2, with 3-benzyloxyaniline, 1-amino-2-methylpropan-2-ol, and 3-methoxypropanoyl chloride used in lieu of 4-benzyloxyaniline, propylamine, and ethoxyacetyl chloride, respectively. The general methods described in Parts H through J of Example 1 were used to convert [7-benzyloxy-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol to 4-amino-1-(2-hydroxy-2-methylpropyl)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-7-ol. A mixture of 4-amino-1-(2-hydroxy-2-methylpropyl)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-7-ol (375 mg, 1.13 mmol), 2-bromomethyl-1,3-dioxolane (208 mg, 1.24 mmol) and potassium carbonate (312 mg, 2.26 mmol) in DMF (15 mL) was heated at 70° C. overnight. The temperature was increased to 130° C. and additional 2-bromomethyl-1,3-dioxolane and potassium carbonate were added over 3 days. The reaction mixture was allowed to cool to room temperature, then was filtered to remove the solids. The filtrate was concentrated under reduced pressure and the residue was slurried in dichloromethane. Again, the solids were removed by filtration and the filtrate was concentrated under reduced pressure. Purification by chromatography on a HORIZON HPFC system (silica gel, gradient elution with 0-35% methanol/dichloromethane (20:80) in dichloromethane) followed by recrystallization from acetonitrile provide 20 mg of 1-[4-amino-7-(1,3-dioxolan-2-ylmethoxy)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol as off white crystals, mp 131.0-136.0° C.

후처리

  1. temperatureThe temperature was increased to 130° C.
  2. temperatureto cool to room temperature
  3. filtrationwas filtered
  4. customto remove the solids
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customAgain, the solids were removed by filtration
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customPurification by chromatography
  9. washon a HORIZON HPFC system (silica gel, gradient elution with 0-35% methanol/dichloromethane (20:80) in dichloromethane)
  10. customfollowed by recrystallization from acetonitrile

출처 및 근거

ORD 기록
ord-3f0a258a5a7642c883bac48bdccdf262
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09365567B2

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