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 1803263Notes

Reaction equation

HRID 1803263 reaction equation
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

Participants

5

Reactant 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

Product 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-amineYield 57%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-606fec46c6c54db788ee1c0cdf348961
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

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