3,4-Difluoro-2-(2-fluoro-4-iodoanilino)benzoyl fluoride → HCID 59469195, compound
Reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[C:8]1([OH:12])[CH2:11][NH:10][CH2:9]1.[F:13][C:14]1[C:15]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([I:31])=[CH:27][C:26]=2[F:32])=[C:16]([CH:20]=[CH:21][C:22]=1[F:23])[C:17](F)=[O:18]>>[F:13][C:14]1[C:15]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([I:31])=[CH:27][C:26]=2[F:32])=[C:16]([C:17]([N:10]2[CH2:11][C:8]([C@@H:3]3[CH2:4][CH2:5][CH2:6][CH2:7][C@@H:2]3[OH:1])([OH:12])[CH2:9]2)=[O:18])[CH:20]=[CH:21][C:22]=1[F:23]Participants
Procedure
The compounds of examples 25a and 25b were synthesized starting from benzyl 3-hydroxy-3-(2-oxycyclohenyl)azetidine-1-carboxylate prepared according to the procedure given in example 25. The ketone was reduced to give benzyl 3-hydroxy-3-(2-hydroxycyclohexyl)azetidine-1-carboxylate as a mixture of racemic diastereomers which were subjected to hydrogenation to afford 3-(2-hydroxycyclohexyl)azetidin-3-ol. 3-(2-hydroxycyclohexyl)azetidin-3-ol was then carried forward in a coupling step with 3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzoyl fluoride in the usual manner. The coupled material thus obtained was purified by preparative reverse phase HPLC where fraction 1 was tentatively assigned as (±)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(trans)-2-hydroxycyclohexyl]azetidin-3-ol (Example 25a) and fraction 2 was tentatively assigned as (±)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(cis)-2-hydroxycyclohexyl]azetidin-3-ol.
Workup
- customThe coupled material thus obtained
- customwas purified by preparative reverse phase HPLC where fraction 1
Sources & evidence
- ORD record
- ord-254e33cd96694d86b9146e334d762bb8
- Source dataset
- uspto-grants-2010_09
- Patent number
- US07803839B2
Reaction notes
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