7-Bromo-9-(4-fluorophenyl)-1,4-dioxaspiro[4.5]decan-8-on → N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-4-(4-fluorophenyl)-5,7-dihydro-4H-spiro[benzo[d]thiazole-6,2'-[1,3]dioxolan]-2-amine

HRID 1803263노트

반응식

HRID 1803263 반응식
Br[CH:2]1[C:11](=O)[CH:10]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[CH2:9][C:4]2([O:8][CH2:7][CH2:6][O:5]2)[CH2:3]1.[Cl:20][C:21]1[N:22]=[CH:23][N:24]([C:26]2[CH:31]=[CH:30][C:29]([NH:32][C:33]([NH2:35])=[S:34])=[CH:28][C:27]=2[O:36][CH3:37])[CH:25]=1>C(O)C.CCOC(C)=O>[Cl:20][C:21]1[N:22]=[CH:23][N:24]([C:26]2[CH:31]=[CH:30][C:29]([NH:32][C:33]3[S:34][C:2]4[CH2:3][C:4]5([O:8][CH2:7][CH2:6][O:5]5)[CH2:9][CH:10]([C:13]5[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=5)[C:11]=4[N:35]=3)=[CH:28][C:27]=2[O:36][CH3:37])[CH:25]=1

참가 물질

5

반응물 2

HCID 581101137-Bromo-9-(4-fluorophenyl)-1,4-dioxaspiro[4.5]decan-8-onHCID 866498881-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)thiourea

생성물 1

HCID 46864555N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-4-(4-fluorophenyl)-5,7-dihydro-4H-spiro[benzo[d]thiazole-6,2'-[1,3]dioxolan]-2-amine수율 57%

시약·촉매·용매 2

HCID 702Ethanol용매HCID 8857Ethyl Acetate용매

실험 절차

A mixture of 7-bromo-9-(4-fluorophenyl)-1,4-dioxaspiro[4.5]decan-8-on (50 mg, 0.177 mmol, preparation AAC) and 1-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)thiourea (91 mg, 0.276 mmol, from step 4 of preparation A) was heated in ethanol (0.25 mL) at 80° C. for 45 min. The crude reaction was diluted with EtOAc and washed with saturated sodium bicarbonate solution. The organic layer was concentrated in vacuo. The crude product was purified using preparatory TLC (50% acetone/hexanes) to give 54 mg (57% yield) of the titled compound as a white solid. LC-MS (M+H)+ 513.2. 1H NMR (400 MHz, chloroform-d) δ ppm 7.49 (dd, J=11.21, 1.89 Hz, 2 H) 7.15-7.24 (m, 2 H) 7.08 (d, J=8.31 Hz, 1 H) 6.93-7.04 (m, 3 H) 6.58 (dd, J=8.56, 2.27 Hz, 1 H) 4.16-4.33 (m, 1H) 3.89-4.15 (m, 4H) 3.49 (s, 3 H) 3.13 (dd, J=16.37, 3.02 Hz, 1 H) 2.82-2.98 (m, 1H) 1.98-2.32 (m, 2 H).

후처리

  1. customfrom step 4 of preparation A)
  2. customThe crude reaction
  3. washwashed with saturated sodium bicarbonate solution
  4. concentrationThe organic layer was concentrated in vacuo
  5. customThe crude product was purified

출처 및 근거

ORD 기록
ord-606fec46c6c54db788ee1c0cdf348961
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08349880B2

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