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 2106562Notes

Reaction equation

HRID 2106562 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[NH:12][C:11](=[O:13])[N:10]([CH:14]3[CH2:19][CH2:18][N:17]([C:20]([O:22][C@H:23]([CH2:42][C:43]4[CH:48]=[C:47]([C:49]([F:52])([F:51])[F:50])[C:46]([NH2:53])=[C:45]([Cl:54])[CH:44]=4)[C:24]([N:26]4[CH2:31][CH2:30][CH:29]([CH:32]5[CH2:37][CH2:36][N:35]([CH2:38][C:39]([OH:41])=[O:40])[CH2:34][CH2:33]5)[CH2:28][CH2:27]4)=[O:25])=[O:21])[CH2:16][CH2:15]3)[CH2:9][CH2:8][C:7]=2[CH:55]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)CC)C.[N:85]1([CH2:91][CH2:92]O)[CH2:90][CH2:89][O:88][CH2:87][CH2:86]1.C([O-])(O)=O.[Na+]>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[NH:12][C:11](=[O:13])[N:10]([CH:14]3[CH2:15][CH2:16][N:17]([C:20]([O:22][C@H:23]([CH2:42][C:43]4[CH:48]=[C:47]([C:49]([F:52])([F:50])[F:51])[C:46]([NH2:53])=[C:45]([Cl:54])[CH:44]=4)[C:24]([N:26]4[CH2:31][CH2:30][CH:29]([CH:32]5[CH2:37][CH2:36][N:35]([CH2:38][C:39]([O:41][CH2:92][CH2:91][N:85]6[CH2:90][CH2:89][O:88][CH2:87][CH2:86]6)=[O:40])[CH2:34][CH2:33]5)[CH2:28][CH2:27]4)=[O:25])=[O:21])[CH2:18][CH2:19]3)[CH2:9][CH2:8][C:7]=2[CH:55]=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

A mixture 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 (Example 15.1), 113 mg (0.35 mmol) TBTU, 84 μL (0.60 mmol) triethylamine and 39.3 mg (0.30 mmol) 2-morpholin-4-yl-ethanol in 5 mL DMF was stirred overnight at RT. The reaction mixture was poured onto saturated NaHCO3 solution, the product precipitated was suction filtered and dried at 40° C. This was dissolved in 25 mL of isopropanol and precipitated as the hydrochloride salt by the addition of 0.5 M HCl in isopropanol. This was suction filtered, washed with 5 mL isopropanol and 30 mL DIPE and dried at 30° C. in the vacuum drying cupboard.

Workup

  1. customthe product precipitated
  2. filtrationfiltered
  3. customdried at 40° C
  4. dissolutionThis was dissolved in 25 mL of isopropanol
  5. customprecipitated as the hydrochloride salt by the addition of 0.5 M HCl in isopropanol
  6. filtrationThis was suction filtered
  7. washwashed with 5 mL isopropanol and 30 mL DIPE
  8. customdried at 30° C. in the vacuum
  9. customdrying cupboard

Sources & evidence

ORD record
ord-0568035ee73e4fd4aab03b03e4bc6d6a
Source dataset
uspto-grants-2009_08
Patent number
US07579341B2

Reaction notes

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