Triethylamine → (R)-1-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-2-[1'-(2-morpholin-4-yl-ethoxycarbonyl-methyl)-4,4'-bipiperidinyl-1-yl]-2-oxo-ethyl 4-(7-methoxy-2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

HRID 2106536Notes

Reaction equation

HRID 2106536 reaction equation
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)CC)C.[N:30]1([CH2:36][CH2:37][OH:38])[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1.[CH3:39][O:40][C:41]1[CH:42]=[CH:43][C:44]2[NH:50][C:49](=[O:51])[N:48]([CH:52]3[CH2:57][CH2:56][N:55]([C:58]([O:60][C@H:61]([CH2:80][C:81]4[CH:86]=[C:85]([C:87]([F:90])([F:89])[F:88])[C:84]([NH2:91])=[C:83]([Cl:92])[CH:82]=4)[C:62]([N:64]4[CH2:69][CH2:68][CH:67]([CH:70]5[CH2:75][CH2:74][N:73]([CH2:76][C:77](O)=[O:78])[CH2:72][CH2:71]5)[CH2:66][CH2:65]4)=[O:63])=[O:59])[CH2:54][CH2:53]3)[CH2:47][CH2:46][C:45]=2[CH:93]=1.C([O-])(O)=O.[Na+]>CN(C=O)C>[CH3:39][O:40][C:41]1[CH:42]=[CH:43][C:44]2[NH:50][C:49](=[O:51])[N:48]([CH:52]3[CH2:53][CH2:54][N:55]([C:58]([O:60][C@H:61]([CH2:80][C:81]4[CH:86]=[C:85]([C:87]([F:90])([F:88])[F:89])[C:84]([NH2:91])=[C:83]([Cl:92])[CH:82]=4)[C:62]([N:64]4[CH2:65][CH2:66][CH:67]([CH:70]5[CH2:75][CH2:74][N:73]([CH2:76][C:77]([O:38][CH2:37][CH2:36][N:30]6[CH2:35][CH2:34][O:33][CH2:32][CH2:31]6)=[O:78])[CH2:72][CH2:71]5)[CH2:68][CH2:69]4)=[O:63])=[O:59])[CH2:56][CH2:57]3)[CH2:47][CH2:46][C:45]=2[CH:93]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 611632-MorpholinoethanolHCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 57807665(R)-1-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-2-(1'-carboxymethyl-4,4'-bipiperidinyl-1-yl)-2-oxo-ethyl 4-(7-methoxy-2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

Product 1

HCID 57807720(R)-1-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-2-[1'-(2-morpholin-4-yl-ethoxycarbonyl-methyl)-4,4'-bipiperidinyl-1-yl]-2-oxo-ethyl 4-(7-methoxy-2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

113 mg (0.35 mmol) TBTU, 84 μL (0.60 mmol) triethylamine and 39 mg (0.30 mmol) 2-morpholin-4-yl-ethanol were added to a solution of 230 mg (0.29 mmol) (R)-1-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-2-(1′-carboxymethyl-4,4′-bipiperidinyl-1-yl)-2-oxo-ethyl 4-(7-methoxy-2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate in 5 mL DMF and the reaction mixture was stirred overnight at RT. The reaction solution was poured onto a saturated NaHCO3 solution, the product precipitated was suction filtered and dried at 40° C. The crude product was dissolved in 25 mL dry isopropanol and precipitated with 0.5 M HCl in isopropanol as the salt. The precipitate was filtered off, washed with 5 mL isopropanol and 30 mL DIPE and dried overnight in the vacuum drying cupboard at 30° C.

Workup

  1. customthe product precipitated
  2. filtrationfiltered
  3. customdried at 40° C
  4. dissolutionThe crude product was dissolved in 25 mL dry isopropanol
  5. customprecipitated with 0.5 M HCl in isopropanol as the salt
  6. filtrationThe precipitate was filtered off
  7. washwashed with 5 mL isopropanol and 30 mL DIPE
  8. customdried overnight in the vacuum
  9. customdrying cupboard at 30° C.

Sources & evidence

ORD record
ord-35b023b665de4deeb644b3341ab5300a
Source dataset
uspto-grants-2009_08
Patent number
US07579341B2

Reaction notes

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