Potassium Carbonate → Methyl 4-(4-(dibutylcarbamoyl)-1-(3-hydroxypropyl)-1H-imidazol-2-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate

HRID 529002노트

반응식

HRID 529002 반응식
[CH2:1]([N:5]([CH2:35][CH2:36][CH2:37][CH3:38])[C:6]([C:8]1[N:9]=[C:10]([C:13]2[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][C:14]=2[C:23]([N:25]2[CH2:34][CH2:33][C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH2:26]2)=[O:24])[NH:11][CH:12]=1)=[O:7])[CH2:2][CH2:3][CH3:4].C([O-])([O-])=O.[K+].[K+].Br[CH2:46][CH2:47][CH2:48][OH:49]>CN(C=O)C.CC(OC)(C)C>[CH2:35]([N:5]([CH2:1][CH2:2][CH2:3][CH3:4])[C:6]([C:8]1[N:9]=[C:10]([C:13]2[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][C:14]=2[C:23]([N:25]2[CH2:34][CH2:33][C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH2:26]2)=[O:24])[N:11]([CH2:46][CH2:47][CH2:48][OH:49])[CH:12]=1)=[O:7])[CH2:36][CH2:37][CH3:38]

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 123083-Bromo-1-propanolHCID 178449064HCID 178449064, 화합물

생성물 1

HCID 71062328Methyl 4-(4-(dibutylcarbamoyl)-1-(3-hydroxypropyl)-1H-imidazol-2-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate수율 32%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 15413tert-Butyl methyl ether용매

반응 조건

온도
40 °C

실험 절차

To a stirred solution of methyl 4-(4-(dibutylcarbamoyl)-1H-imidazol-2-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate (200 mg, 0.38 mmol) in DMF (8 mL) was added K2CO3 (107 mg, 0.77 mmol) and 3-bromopropanol (54 mg, 0.38 mmol). The reaction mixture was heated at 40° C. for 4 h, cooled to room temperature, diluted with MTBE, and quenched with water. The organic layer was separated and the aqueous layer was extracted with MTBE (3×). The combined organic layer was dried over Na2SO4 and concentrated in vacuo to provide crude product. The crude material was purified by flash chromatography (gradient from 10 to 50% EtOAc/hexanes) to provide the title compound (67 mg, 32%). 1H NMR (CDCl3, 1:1 mixture of amide rotamers) δ 8.19-8.15 (m, 1H), 8.04 (dd, J=11.2, 1.6 Hz, 1H), 7.62 (s, 0.5H), 7.55 (s, 0.5H), 7.50-7.46 (m, 1H), 7.25-7.14 (m, 3.5H), 6.94 (d, J=7.2 Hz, 0.5H), 4.84-4.59 (m, 2H), 4.29-4.13 (m, 2H), 3.96 (s, 3H), 3.82-3.70 (m, 2H), 3.50-3.35 (m, 4H), 3.31-2.88 (m, 4H), 1.89-1.87 (m, 2H), 1.55-1.49 (m, 2H), 1.40-1.05 (m, 6H), 0.93-0.88 (m, 3H), 0.74 (t, J=7.2 Hz, 1.5H), 0.65 (t, J=7.2 Hz, 1.5H); MS(ESI+) m/z 575.6 (M+H)+.

후처리

  1. temperaturecooled to room temperature
  2. customquenched with water
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with MTBE (3×)
  5. dry with materialThe combined organic layer was dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customto provide crude product
  8. customThe crude material was purified by flash chromatography (gradient from 10 to 50% EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-b871832571d64e3f9d1dcf21787bf13c
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346795B2

반응 노트

불러오는 중…