Dimethylformamide → HCID 53358940, compound

HRID 1807258Notes

Reaction equation

HRID 1807258 reaction equation
[Cl:1][C:2]1[C:3]([F:31])=[C:4]([CH:8]2[C:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[CH:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10][CH:9]2[C:28]([OH:30])=O)[CH:5]=[CH:6][CH:7]=1.C([N:35]([CH:38](C)C)CC)(C)C.[CH:41]1[CH:42]=[CH:43][C:44]2N(O)N=N[C:45]=2[CH:46]=1.CN([C:54]([O:58]N1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN(C)[CH:77]=[O:78]>>[CH3:77][O:78][C:54]([CH:41]1[CH2:42][CH2:43][CH:44]([CH2:38][NH:35][C:28]([C@H:9]2[C@H:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=3[F:31])[C@:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:25])([CH3:26])[CH3:27])[NH:10]2)=[O:30])[CH2:45][CH2:46]1)=[O:58]

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 666882513-(3-Chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid

Product 1

HCID 53358940HCID 53358940, compoundYield 79%

Procedure

To a stirred solution of rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (61 mg, 0.13 mmol) in N,N-dimethyl formamide (5 mL) was added diisopropylethylamine (126.1 mg, 0.976 mmol), HOBt (35.3 mg, 0.262 mmol), HBTU (97.8 mg, 0.258 mmol) and methyl-trans-4-aminomethyl-cyclohexane carboxylic acid HCl (56.2 mg, 0.256 mmol, AK Scientific). After it was stirred at rt for 2.5 hrs, the solvent was removed and the reaction mixture was extracted with EtOAc and washed with 1N NaOH (2×), water, and saturated NaCl. The organic phase was separated and dried over Na2SO4. The reaction mixture was then purified by flash column to give rac 4-({[(2R,3S,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-methyl)-cyclohexanecarboxylic acid methyl ester (64.0 mg, 79%) and a white solid foam. HRMS (ES+) m/z Calcd C32H37Cl2F2N3O3+H [(M+H): 620.2253. Found: 620.2253.

Workup

  1. customthe solvent was removed
  2. extractionthe reaction mixture was extracted with EtOAc
  3. washwashed with 1N NaOH (2×), water, and saturated NaCl
  4. customThe organic phase was separated
  5. dry with materialdried over Na2SO4
  6. customThe reaction mixture was then purified by flash column

Sources & evidence

ORD record
ord-29127735b1f8464db5b120a8a07ef243
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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