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Hydrochloric Acid → 1-[4-amino-2-ethoxymethyl-7-(thiazol-4-ylmethoxy)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol

HRID 2383187
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HRID 2383187 반응식
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:20][O:21][CH2:22][CH3:23])[N:14]([CH2:15][C:16]([OH:19])([CH3:18])[CH3:17])[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([OH:24])=[CH:5][C:4]=2[N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:32][C:33]1[N:34]=[CH:35][S:36][CH:37]=1.Cl>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C.C(N(CC)CC)C>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:20][O:21][CH2:22][CH3:23])[N:14]([CH2:15][C:16]([CH3:18])([OH:19])[CH3:17])[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([O:24][CH2:32][C:33]3[N:34]=[CH:35][S:36][CH:37]=3)=[CH:5][C:4]=2[N:3]=1
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참가 물질

8

반응물 4

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 27632904-(Chloromethyl)-1,3-thiazoleHCID 1363405384-amino-2-ethoxymethyl-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-ol

생성물 1

HCID 575453141-[4-amino-2-ethoxymethyl-7-(thiazol-4-ylmethoxy)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol

시약·촉매·용매 3

HCID 74236
Tetrabutylammonium Bromide
촉매
HCID 6228Dimethylformamide용매
HCID 8471Triethylamine용매

실험 절차

4-Amino-2-ethoxymethyl-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-ol (100 mg, 0.3 mmol), cesium carbonate (488 mg, 1.5 mmol), 4-(chloromethyl)thiazole.HCl (102 mg, 0.6 mmol), tetrabutylammonium bromide (96 mg, 0.3 mmol), triethylamine (0.5 ml), and DMF (10 mL) were combined and stirred at ambient temperature overnight. The reaction was concentrated under reduced pressure and dichloromethane was added to the residue. Undissolved solids were removed by filtration. The filtrate was concentrated under reduced pressure and subsequently purified by flash column chromatography on silica gel, eluting with a gradient of 0-4% methanol in dichloromethane. The clean fractions were combined and concentrated under reduced pressure. The resulting solid was recrystallized from acetonitrile to yield 62 mg of 1-[4-amino-2-ethoxymethyl-7-(thiazol-4-ylmethoxy)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol as a white powder, mp 190.0-191.0° C.

후처리

  1. concentrationThe reaction was concentrated under reduced pressure and dichloromethane
  2. additionwas added to the residue
  3. customwere removed by filtration
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customsubsequently purified by flash column chromatography on silica gel
  6. washeluting with a gradient of 0-4% methanol in dichloromethane
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting solid was recrystallized from acetonitrile

출처 및 근거

ORD 기록
ord-a9d8b4165c854fdcb009988c7f438a4e
출처 데이터셋
uspto-grants-2012_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08263594B2

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