Triethylamine → (R)-1-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-2-[4-((R)-2-dimethylcarbamoylmethoxycarbonyl-pyrrolidin-1-yl)-piperidin-1-yl]-2-oxo-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

HRID 2267241Notes

Reaction equation

HRID 2267241 reaction equation
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)CC)C.[O:30]=[C:31]1[N:37]([CH:38]2[CH2:43][CH2:42][N:41]([C:44]([O:46][C@H:47]([CH2:64][C:65]3[CH:70]=[C:69]([C:71]([F:74])([F:73])[F:72])[C:68]([NH2:75])=[C:67]([Cl:76])[CH:66]=3)[C:48]([N:50]3[CH2:55][CH2:54][CH:53]([N:56]4[CH2:60][CH2:59][CH2:58][C@@H:57]4[C:61]([OH:63])=[O:62])[CH2:52][CH2:51]3)=[O:49])=[O:45])[CH2:40][CH2:39]2)[CH2:36][CH2:35][C:34]2[CH:77]=[CH:78][CH:79]=[CH:80][C:33]=2[NH:32]1.O[CH2:82][C:83]([N:85]([CH3:87])[CH3:86])=[O:84]>CN(C=O)C>[O:30]=[C:31]1[N:37]([CH:38]2[CH2:43][CH2:42][N:41]([C:44]([O:46][C@H:47]([CH2:64][C:65]3[CH:70]=[C:69]([C:71]([F:72])([F:74])[F:73])[C:68]([NH2:75])=[C:67]([Cl:76])[CH:66]=3)[C:48]([N:50]3[CH2:51][CH2:52][CH:53]([N:56]4[CH2:60][CH2:59][CH2:58][C@@H:57]4[C:61]([O:63][CH2:82][C:83](=[O:84])[N:85]([CH3:87])[CH3:86])=[O:62])[CH2:54][CH2:55]3)=[O:49])=[O:45])[CH2:40][CH2:39]2)[CH2:36][CH2:35][C:34]2[CH:77]=[CH:78][CH:79]=[CH:80][C:33]=2[NH:32]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 128746822-Hydroxy-N,N-dimethylacetamideHCID 16045960(R)-1-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-2-[4-((R)-2-carboxy-pyrrolidin-1-yl)-piperidin-1-yl]-2-oxo-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

Product 1

HCID 57807318(R)-1-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-2-[4-((R)-2-dimethylcarbamoylmethoxycarbonyl-pyrrolidin-1-yl)-piperidin-1-yl]-2-oxo-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

25 mg (0.08 mmol) TBTU and 11 μL (0.08 mmol) triethylamine were added to a solution of 50 mg (0.07 mmol) (R)-1-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-2-[4-((R)-2-carboxy-pyrrolidin-1-yl)-piperid in-1-yl]-2-oxo-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate in 1 mL DMF and stirred for 10 min at RT. 8.1 mg (0.08 mmol) 2-hydroxy-N,N-dimethyl -acetamide were added to the reaction mixture and this was shaken overnight at RT. After filtration through a syringe filter the reaction solution was purified by HPLC without further working up. The fractions containing the product were combined and freeze-dried.

Workup

  1. stirringthis was shaken overnight at RT
  2. filtrationAfter filtration through a syringe
  3. filtrationfilter the reaction solution
  4. customwas purified by HPLC
  5. additionThe fractions containing the product
  6. customfreeze-dried

Sources & evidence

ORD record
ord-c8fa13fb7c664724855d3b6f636cfa8e
Source dataset
uspto-grants-2010_12
Patent number
US07858622B2

Reaction notes

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