Triethylamine → (R)-1-(4-hydroxy-3,5-dimethyl-benzyl)-2-[4-(4-methyl-tetrahydropyran-4-yl)-piperazin-1-yl]-2-oxo-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

HRID 643109Notes

Reaction equation

HRID 643109 reaction equation
[CH3:1][C:2]1([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH2:7][CH2:6][O:5][CH2:4][CH2:3]1.[O:14]=[C:15]1[N:21]([CH:22]2[CH2:27][CH2:26][N:25]([C:28]([O:30][C@@H:31]([C:42](O)=[O:43])[CH2:32][C:33]3[CH:38]=[C:37]([CH3:39])[C:36]([OH:40])=[C:35]([CH3:41])[CH:34]=3)=[O:29])[CH2:24][CH2:23]2)[CH2:20][CH2:19][C:18]2[CH:45]=[CH:46][CH:47]=[CH:48][C:17]=2[NH:16]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)CC)C.C([O-])(O)=O.[Na+]>CN(C=O)C>[O:14]=[C:15]1[N:21]([CH:22]2[CH2:23][CH2:24][N:25]([C:28]([O:30][C@H:31]([CH2:32][C:33]3[CH:34]=[C:35]([CH3:41])[C:36]([OH:40])=[C:37]([CH3:39])[CH:38]=3)[C:42]([N:11]3[CH2:10][CH2:9][N:8]([C:2]4([CH3:1])[CH2:7][CH2:6][O:5][CH2:4][CH2:3]4)[CH2:13][CH2:12]3)=[O:43])=[O:29])[CH2:26][CH2:27]2)[CH2:20][CH2:19][C:18]2[CH:45]=[CH:46][CH:47]=[CH:48][C:17]=2[NH:16]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 576741111-(4-Methyloxan-4-yl)piperazineHCID 67273812HCID 67273812, compound

Product 1

HCID 11858159(R)-1-(4-hydroxy-3,5-dimethyl-benzyl)-2-[4-(4-methyl-tetrahydropyran-4-yl)-piperazin-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

50 mg (0.23 mmol) 1-(4-methyl-tetrahydropyran-4-yl)-piperazine (amine A1, used as the hydrochloride salt) were added to a solution of 90 mg (0.19 mmol) (R)-2-(4-hydroxy-3,5-dimethyl-phenyl)-1-carboxy-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate (Example 7h), 70 mg (0.22 mmol) TBTU and 70 μL (0.50 mmol) triethylamine in 1 mL DMF and the reaction mixture was stirred for 20 h at RT. Semisaturated NaHCO3 solution was added, the precipitate was filtered off and dried. The purification was carried out by chromatography (Alox, activity stage II-III, DCM/MeOH 30:1). After the solvent had been eliminated the residue was triturated with diethyl ether, suction filtered and dried.

Workup

  1. filtrationthe precipitate was filtered off
  2. customdried
  3. customThe purification
  4. customwas triturated with diethyl ether, suction
  5. filtrationfiltered
  6. customdried

Sources & evidence

ORD record
ord-e7ba3bf6b334419bb7987d4df5391e26
Source dataset
uspto-grants-2010_04
Patent number
US07696209B2

Reaction notes

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