Triethylamine → (R)-1-(4-methyl-2-oxo-2,3-dihydro-benzoxazol-6-ylmethyl)-2-oxo-2-(4-oxo-piperidin-1-yl)-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

HRID 1864620Notes

Reaction equation

HRID 1864620 reaction equation
[NH:1]1[CH2:6][CH2:5][C:4](=[O:7])[CH2:3][CH2:2]1.[O:8]=[C:9]1[N:15]([CH:16]2[CH2:21][CH2:20][N:19]([C:22]([O:24][C@@H:25]([C:38](O)=[O:39])[CH2:26][C:27]3[CH:36]=[C:35]([CH3:37])[C:30]4[NH:31][C:32](=[O:34])[O:33][C:29]=4[CH:28]=3)=[O:23])[CH2:18][CH2:17]2)[CH2:14][CH2:13][C:12]2[CH:41]=[CH:42][CH:43]=[CH:44][C:11]=2[NH:10]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)CC)C>CN(C=O)C>[O:8]=[C:9]1[N:15]([CH:16]2[CH2:17][CH2:18][N:19]([C:22]([O:24][C@H:25]([CH2:26][C:27]3[CH:36]=[C:35]([CH3:37])[C:30]4[NH:31][C:32](=[O:34])[O:33][C:29]=4[CH:28]=3)[C:38](=[O:39])[N:1]3[CH2:6][CH2:5][C:4](=[O:7])[CH2:3][CH2:2]3)=[O:23])[CH2:20][CH2:21]2)[CH2:14][CH2:13][C:12]2[CH:41]=[CH:42][CH:43]=[CH:44][C:11]=2[NH:10]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 337214-PiperidoneHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 68608307(R)-1-carboxy-2-(4-methyl-2-oxo-2,3-dihydrobenzoxazol-6-yl)-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

Product 1

HCID 69058954(R)-1-(4-methyl-2-oxo-2,3-dihydro-benzoxazol-6-ylmethyl)-2-oxo-2-(4-oxo-piperidin-1-yl)-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

200 mg (1.30 mmol) piperidin-4-one (used as the hydrate of the hydrochloride salt) were added to a solution of 500 mg (0.98 mmol) (R)-1-carboxy-2-(4-methyl-2-oxo-2,3-dihydrobenz-oxazol-6-yl)-ethyl 4-(2-oxo-1,2,4,5,-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate, 350 mg (1.09 mmol) TBTU, 300 μL (2.15 mmol) triethylamine in 10 mL DMF and the reaction mixture was stirred for 4 h at RT. The reaction solution was evaporated down i. vac., the residue was taken up in DCM, the organic phase was washed with saturated NaHCO3 solution and dried on Na2SO4. After the desiccant and solvent had been eliminated the residue was purified by chromatography (silica gel, gradient DCM/MeOH 20:1 to DCM/MeOH 10:1). The fractions containing the product were concentrated by evaporation, the residue was stirred with DIPE, suction filtered and dried.

Workup

  1. customThe reaction solution was evaporated down i
  2. washthe organic phase was washed with saturated NaHCO3 solution
  3. customdried on Na2SO4
  4. customwas purified by chromatography (silica gel, gradient DCM/MeOH 20:1 to DCM/MeOH 10:1)
  5. additionThe fractions containing the product
  6. concentrationwere concentrated by evaporation
  7. stirringthe residue was stirred with DIPE, suction
  8. filtrationfiltered
  9. customdried

Sources & evidence

ORD record
ord-b68cb5cac5454edd87d355d890085329
Source dataset
uspto-grants-2009_12
Patent number
US07625886B2

Reaction notes

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