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 1803263ノート

反応式

HRID 1803263 の反応式
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

参加物

5

反応物 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

生成物 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-amine収率 57%

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-606fec46c6c54db788ee1c0cdf348961
出典データセット
uspto-grants-2013_01
特許番号
US08349880B2

反応ノート

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