Diisopropylethylamine → rac-(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-1-(6-morpholin-4-yl-pyridine-3-sulfonyl)-pyrrolidine-3-carbonitrile

HRID 909085Notes

Reaction equation

HRID 909085 reaction equation
[Cl:1][C:2]1[C:3]([F:28])=[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])[CH2:10][NH:9]2)[CH:5]=[CH:6][CH:7]=1.CCN(C(C)C)C(C)C.[N:38]1([C:44]2[N:49]=[CH:48][C:47]([S:50](Cl)(=[O:52])=[O:51])=[CH:46][CH:45]=2)[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1>C(Cl)Cl>[Cl:1][C:2]1[C:3]([F:28])=[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]([CH3:25])([CH3:27])[CH3:26])[CH2:10][N:9]2[S:50]([C:47]2[CH:48]=[N:49][C:44]([N:38]3[CH2:39][CH2:40][O:41][CH2:42][CH2:43]3)=[CH:45][CH:46]=2)(=[O:52])=[O:51])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 81531Diisopropylethylamine2×HCID 27764626-Morpholin-4-yl-pyridine-3-sulfonyl chloride2×HCID 67095372rac-(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile

Product 1

HCID 67095374rac-(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-1-(6-morpholin-4-yl-pyridine-3-sulfonyl)-pyrrolidine-3-carbonitrileYield 35.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of rac-(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile (35.4 mg, 0.084 mmol) in CH2Cl2 (3 mL) was added DIPEA (44.5 mg, 0.344 mmol) and 6-morpholin-4-yl-pyridine-3-sulfonyl chloride (45.0 mg, 0.171 mmol, Maybridge). It was stirred at rt for 3.5 hrs under argon. More DIPEA (29.7 mg, 0.230 mmol) and 6-morpholin-4-yl-pyridine-3-sulfonyl chloride (18.7 mg, 0.071 mmol, Maybridge) were added. After 1.75 hrs the reaction mixture was extracted with EtOAc, washed with water, saturated sodium bicarbonate, 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-(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-1-(6-morpholin-4-yl-pyridine-3-sulfonyl)-pyrrolidine-3-carbonitrile (19.4 mg, 35.7%). HRMS (ES+) m/z Calcd for C31H32Cl2F2N4O3S H [(M+H)+]: 649.1613; Found: 649.1615.

Workup

  1. extractionAfter 1.75 hrs the reaction mixture was extracted with EtOAc
  2. washwashed with water, saturated sodium bicarbonate, water, and saturated NaCl
  3. customThe organic phase was separated
  4. dry with materialdried over Na2SO4
  5. customThe reaction mixture was then purified by flash column

Sources & evidence

ORD record
ord-b97f4751cb4f4b2784b68ebc96144d72
Source dataset
uspto-grants-2011_09
Patent number
US08017607B2

Reaction notes

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