Trifluoroacetic acid → HCID 10109051, compound

HRID 2308220Notes

Reaction equation

HRID 2308220 reaction equation
[C:1]([NH:11][C@H:12]([C:17]([OH:19])=O)[C@H:13]([CH2:15][CH3:16])[CH3:14])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].CCN=C=[N:24][CH2:25][CH2:26][CH2:27][N:28]([CH3:30])[CH3:29].[N:31]#CN.C(O)(C(F)(F)F)=O.BrC#N>C(Cl)Cl.CN(C1C=CN=CC=1)C.CCOC(C)=O>[C:30]([N:28]1[CH2:27][CH:26]([CH2:25][NH:24][C:17]([C@@H:12]([NH:11][C:1](=[O:2])[O:3][CH2:4][C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=2)[C@@H:13]([CH3:14])[CH2:15][CH3:16])=[O:19])[CH2:29]1)#[N:31]

Participants

9

Reactant 5

HCID 6422Trifluoroacetic acidHCID 9864CyanamideHCID 10476Cyanogen BromideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 2724772N-[(Phenylmethoxy)carbonyl]-L-isoleucine

Product 1

HCID 10109051HCID 10109051, compound

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Following general procedure 9, to a stirred solution of the amine (48) (186 mg, 1 equiv.), N-carbobenzyloxy-L-isoleucine (265 mg, 1 equiv.) and EDCI (211 mg, 1.1 equiv.) in CH2Cl2 (5 mL) was added DMAP (61 mg, 0.5 equiv.). The resultant mixture was stirred at rt for 16 h. The mixture was then diluted with EtOAc and washed successively with 10% citric acid, H2O and brine. The organic extract was dried (MgSO4) and concentrated under reduced pressure. The residue was purified by flash chromatography (gradient elution: 30% EtOAc in hexane to 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 afford the desired solid benzyl (1S,2S)-1-({[(1-cyano-3-azetidinyl)methyl]amino}carbonyl)-2-methylbutylcarbamate (51).

Workup

  1. washwashed successively with 10% citric acid, H2O and brine
  2. extractionThe organic extract
  3. dry with materialwas dried (MgSO4)
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash chromatography (gradient elution: 30% EtOAc in hexane to 50% EtOAc in hexane)
  6. customto afford the
  7. customThe crude material was purified by flash chromatography (gradient elution: 50% EtOAc in hexane)

Sources & evidence

ORD record
ord-ebed5fae99654bc7b5e713f83409bf0a
Source dataset
uspto-grants-2004_12
Patent number
US06835727B2

Reaction notes

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