Trifluoroacetic acid → HCID 22601244, compound

HRID 2308216Notes

Reaction equation

HRID 2308216 reaction equation
[CH3:1][CH2:2][N:3](CC)CC.[C:8](Br)(=[O:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[N:17]#[C:18][NH2:19].[C:20](O)([C:22](F)(F)F)=O.BrC#N>C(Cl)Cl>[C:18]([N:19]1[CH2:22][CH2:20][CH:2]([NH:3][C:8](=[O:15])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:1]1)#[N:17].[N:17]#[C:18][NH2:19]

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 9864CyanamideHCID 10476Cyanogen BromideHCID 12056Benzoyl bromide

Product 1

HCID 22601244HCID 22601244, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of the benzyl carbamate intermediate (34) (1.95 g, 1 equiv.) in MeOH (20 mL) was added palladium on carbon (200 mg, 10%). The solution was evacuated, placed under a H2 atmosphere (35 atm) and shaken for 5 h. The suspension was then filtered through celite and washed with MeOH. The filtrate was concentrated under reduced pressure to afford the desired amine. Following general procedure 10, to a stirred solution of this amine (105 mg, 1 equiv.) and Et3N (160 uL, 2 equiv.) in CH2Cl2 (5 mL) was added benzoyl bromide (90 uL, 1.3 equiv.). The resultant mixture was stirred at rt for 10 min. The mixture was concentrated under reduced pressure and the residue was purified by flash chromatography (50% EtOAc in hexane) to afford the desired coupled product. The N-Boc group of the coupled product was then converted to the cyanamide (N—CN) following general procedure 3 (i.e. successive treatment with TFA and BrCN). The crude material was purified by flash chromatography (gradient elution: 50% EtOAc in hexane to 67% EtOAc in hexane) to afford the desired cyanamide N-(1-cyano-3-pyrrolidinyl)benzamide (36).

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. customthe residue was purified by flash chromatography (50% EtOAc in hexane)
  3. customto afford the
  4. customThe crude material was purified by flash chromatography (gradient elution: 50% EtOAc in hexane to 67% EtOAc in hexane)

Sources & evidence

ORD record
ord-55620955e2e345c2b60860e8f00e3af0
Source dataset
uspto-grants-2004_12
Patent number
US06835727B2

Reaction notes

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