Ammonia → (S)-3-[N-{3,5-bis(trifluoromethyl)benzoyl}glycyl]amino-1-(4-chlorobenzyl)pyrrolidine

HRID 1280948Notes

Reaction equation

HRID 1280948 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=1)[C:6](Cl)=[O:7].[Cl:18][C:19]1[CH:35]=[CH:34][C:22]([CH2:23][N:24]2[CH2:28][CH2:27][C@H:26]([NH:29][C:30](=[O:33])[CH2:31][NH2:32])[CH2:25]2)=[CH:21][CH:20]=1.C(N(CC)CC)C.N>C(Cl)(Cl)Cl>[F:1][C:2]([F:17])([F:16])[C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=1)[C:6]([NH:32][CH2:31][C:30]([NH:29][C@H:26]1[CH2:27][CH2:28][N:24]([CH2:23][C:22]2[CH:21]=[CH:20][C:19]([Cl:18])=[CH:35][CH:34]=2)[CH2:25]1)=[O:33])=[O:7]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 8471TriethylamineHCID 1018563,5-Bis(trifluoromethyl)benzoyl chlorideHCID 54551711HCID 54551711, compound

Product 1

HCID 86757903(S)-3-[N-{3,5-bis(trifluoromethyl)benzoyl}glycyl]amino-1-(4-chlorobenzyl)pyrrolidine

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

A solution of 3,5-bis(trifluoromethyl)benzoyl chloride (0.060 mmol) in chloroform (0.4 mL) was added to a solution of (S)-1-(4-chlorobenzyl)-3-(glycylamino)pyrrolidine (0.050 mmol) and triethylamine (0.070 mmol) in chloroform (1.0 mL). After the reaction mixture was agitated at room temperature for 2.5 h, (aminomethyl)polystyrene resin (1.04 mmol/g, 50 mg, 50 mmol) was added and the mixture was agitated at room temperature for 12 h. The reaction mixture was filtered and the resin was washed with dichloromethane (0.5 mL). The filtrate and washing were combined, dichloromethane (4 mL) was added, and the solution was washed with 2 N aqueous NaOH solution (0.5 mL) to give (S)-3-[N-{3,5-bis(trifluoromethyl)benzoyl}glycyl]amino-1-(4-chlorobenzyl)pyrrolidine (compound No. 5) (14.4 mg, 57%): The purity was determined by RPLC/MS (97%); ESI/MS m/e 508.0 (M++H, C22H20ClF6N3O2).

Workup

  1. stirringthe mixture was agitated at room temperature for 12 h
  2. filtrationThe reaction mixture was filtered
  3. washthe resin was washed with dichloromethane (0.5 mL)
  4. washThe filtrate and washing
  5. additiondichloromethane (4 mL) was added
  6. washthe solution was washed with 2 N aqueous NaOH solution (0.5 mL)

Sources & evidence

ORD record
ord-c7377821a9c04ecf8734f89025193846
Source dataset
uspto-grants-2002_09
Patent number
US06451842B1

Reaction notes

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