Ethyl 3-(3-(tert-butylthio)-5-hydroxy-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)-1H-indol-2-yl)-2,2-dimethylpropanoate → 3-[5-Hydroxy-3-(2-methyl-2-propylthio)-1-[4-(2-methoxypyrid-5-yl)benzyl]indol-2-yl]-2,2-dimethylpropionic acid ethyl ester
Reaction equation
C1[N:5]([C@@H:6]2[O:10][C@@H:9]3COP(O)(O[C@H]3[C@H:7]2O)=O)[C:4]2NC(N)=N[C:21](=O)[C:3]=2N=1.[C:24]([S:28][C:29]1[C:37]2[C:32](=[CH:33][CH:34]=[C:35]([OH:38])[CH:36]=2)[N:31]([CH2:39][C:40]2[CH:45]=[CH:44][C:43](B3OC(C)(C)C(C)(C)O3)=[CH:42][CH:41]=2)[C:30]=1[CH2:55][C:56]([CH3:63])([CH3:62])[C:57]([O:59][CH2:60][CH3:61])=[O:58])([CH3:27])([CH3:26])[CH3:25]>>[CH2:60]([O:59][C:57](=[O:58])[C:56]([CH3:62])([CH3:63])[CH2:55][C:30]1[N:31]([CH2:39][C:40]2[CH:41]=[CH:42][C:43]([C:3]3[CH:21]=[CH:7][C:6]([O:10][CH3:9])=[N:5][CH:4]=3)=[CH:44][CH:45]=2)[C:32]2[C:37]([C:29]=1[S:28][C:24]([CH3:26])([CH3:27])[CH3:25])=[CH:36][C:35]([OH:38])=[CH:34][CH:33]=2)[CH3:61]Participants
3
Reactant 2
Product 1
Procedure
The cGMP starting material used for the process was ethyl 3-(3-(tert-butylthio)-5-hydroxy-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)-1H-indol-2-yl)-2,2-dimethylpropionate from Example 3. Ethyl 3-(3-(tert-butylthio)-5-hydroxy-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)-1H-indol-2-yl)-2,2-dimethylpropionate from Example 3, was scaled up to 2.0 kg. In order to ensure optimal Suzuki coupling conditions, the amount of time needed to deoxygenate the mixture was increased from about 5-10 minutes to about 30-45 minutes. Workup and isolation of the product proceeded as described above to yield 1.49 kg of 3-[5-hydroxy-3-(2-methyl-2-propylthio)-1-[4-(2-methoxypyrid-5-yl)benzyl]indol-2-yl]-2,2-dimethylpropionic acid ethyl ester in about 86% yield.