Potassium Carbonate → 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic Acid [(R)-2-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-2-oxo-1-(5,6,7,8-tetrahydro-naphthalen-2-ylmethyl)-ethyl]-amide

HRID 644339Notes

Reaction equation

HRID 644339 reaction equation
[O:1]=[C:2]1[N:8]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([NH:17][C@H:18]([CH2:22][C:23]3[CH:32]=[CH:31][C:30]4[CH2:29][CH2:28][CH2:27][CH2:26][C:25]=4[CH:24]=3)[C:19](O)=[O:20])=[O:16])[CH2:11][CH2:10]2)[CH2:7][CH2:6][C:5]2[CH:33]=[CH:34][CH:35]=[CH:36][C:4]=2[NH:3]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(C(C)C)C(C)C)C.[CH3:68][N:69]1[CH2:74][CH2:73][N:72]([CH:75]2[CH2:80][CH2:79][NH:78][CH2:77][CH2:76]2)[CH2:71][CH2:70]1.C([O-])([O-])=O.[K+].[K+]>C1COCC1>[CH3:68][N:69]1[CH2:74][CH2:73][N:72]([CH:75]2[CH2:80][CH2:79][N:78]([C:19](=[O:20])[C@H:18]([NH:17][C:15]([N:12]3[CH2:11][CH2:10][CH:9]([N:8]4[CH2:7][CH2:6][C:5]5[CH:33]=[CH:34][CH:35]=[CH:36][C:4]=5[NH:3][C:2]4=[O:1])[CH2:14][CH2:13]3)=[O:16])[CH2:22][C:23]3[CH:32]=[CH:31][C:30]4[CH2:29][CH2:28][CH2:27][CH2:26][C:25]=4[CH:24]=3)[CH2:77][CH2:76]2)[CH2:71][CH2:70]1

Participants

7

Reactant 5

HCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 7957071-Methyl-4-(piperidin-4-yl)piperazineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 68578837(R)-2-{[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carbonyl]-amino}-3-(5,6,7,8-tetrahydro-naphthalen-2-yl)-propionic acid

Product 1

HCID 103493464-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic Acid [(R)-2-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-2-oxo-1-(5,6,7,8-tetrahydro-naphthalen-2-ylmethyl)-ethyl]-amide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 500 mg (1.02 mmol) (R)-2-{[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carbonyl]-amino}-3-(5,6,7,8-tetrahydro-naphthalen-2-yl)-propionic acid, 350 mg (1.09 mmol) TBTU, 0.19 mL (1.08 mmol) ethyldiisopropylamine and 30 mL THF was stirred for 30 min at RT, then combined with 195 mg (1.06 mmol) 1-methyl-4-piperidin-4-yl-piperazin and stirred overnight. The reaction mixture was poured onto 100 mL of a 15% K2CO3 solution and extracted twice with DCM. The combined organic extracts were dried, evaporated down under reduced pressure and the residue was purified by chromatography on silica gel. The product fractions were evaporated down under reduced pressure, the residue was triturated with diisopropylether, suction filtered and dried.

Workup

  1. stirringstirred overnight
  2. extractionextracted twice with DCM
  3. customThe combined organic extracts were dried
  4. customevaporated down under reduced pressure
  5. customthe residue was purified by chromatography on silica gel
  6. customThe product fractions were evaporated down under reduced pressure
  7. customthe residue was triturated with diisopropylether, suction
  8. filtrationfiltered
  9. customdried

Sources & evidence

ORD record
ord-374e62a2563e480a8802a1ab1418df0a
Source dataset
uspto-grants-2010_04
Patent number
US07700589B2

Reaction notes

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