Ammonia → HCID 508728, compound

HRID 2103658Notes

Reaction equation

HRID 2103658 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[F:11])[C:5](Cl)=[O:6].[Cl:12][C:13]1[CH:29]=[CH:28][C:16]([CH2:17][N:18]2[CH2:22][CH2:21][C@@H:20]([NH:23][C:24](=[O:27])[CH2:25][NH2:26])[CH2:19]2)=[CH:15][CH:14]=1.C(N(CC)CC)C.N>C(Cl)(Cl)Cl>[Cl:12][C:13]1[CH:29]=[CH:28][C:16]([CH2:17][N:18]2[CH2:22][CH2:21][C@@H:20]([NH:23][C:24](=[O:27])[CH2:25][NH:26][C:5](=[O:6])[C:4]3[CH:8]=[CH:9][C:10]([F:11])=[C:2]([F:1])[CH:3]=3)[CH2:19]2)=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 222AmmoniaHCID 8471TriethylamineHCID 27245193,4-Difluorobenzoyl chlorideHCID 54551710(R)-1-(4-chlorobenzyl)-3-(glycylamino)pyrrolidine

Product 1

HCID 508728HCID 508728, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

The chloroform (0.4 mL) solution of 3,4-difluorobenzoyl chloride (0.060 mmol) was added to the chloroform (1.0 mL) solution of the (R)-1-(4-chlorobenzyl)-3-(glycylamino)pyrrolidine (0.050 mmol) and triethylamine (0.070 mmol). The reaction mixture was stirred at room temperature for 2.5 hours, and then mixed with a (aminomethyl)polystyrene resin (1.04 mmol/g, 50 mg, 50 mmol). The mixture was stirred at room temperature for 12 hours, and filtered. The resin was washed with dichloromethane (0.5 mL). The filtrate and the washings were combined and mixed with dichloromethane (4 mL). The solution was washed with a 2M NaOH aqueous solution (0.5 mL), and then concentrated to obtain the (R)-1-(4-chlorobenzyl)-3-[{N-(3,4-difluorobenzoyl)glycyl}amino]pyrrolidine (Compd. No. 69) (7.8 mg, 38%): the purity was determined with RPLC/MS (>99%); ESI/MS m/e 408.0 (M++H, C20H20ClF2N3O2).

Workup

  1. stirringThe mixture was stirred at room temperature for 12 hours
  2. filtrationfiltered
  3. washThe resin was washed with dichloromethane (0.5 mL)
  4. additionmixed with dichloromethane (4 mL)
  5. washThe solution was washed with a 2M NaOH aqueous solution (0.5 mL)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-47f830a7377047c58ba291749e64ca3d
Source dataset
uspto-grants-2009_08
Patent number
US07576117B1

Reaction notes

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