Tetrahydrofuran → 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid-{(R)-1-(3,4-diethyl-benzyl)-2-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-2-oxo-ethyl}-amide

HRID 644297Notes

Reaction equation

HRID 644297 reaction equation
[NH2:1][C@H:2]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][CH3:26])=[C:21]([CH2:27][CH3:28])[CH:20]=1)[C:3]([N:5]1[CH2:10][CH2:9][N:8]([CH:11]2[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]2)[CH2:7][CH2:6]1)=[O:4].[NH:29]1[CH2:34][CH2:33][CH:32]([N:35]2[CH2:41][CH2:40][C:39]3[CH:42]=[CH:43][CH:44]=[CH:45][C:38]=3[NH:37][C:36]2=[O:46])[CH2:31][CH2:30]1.C1C[O:50][CH2:49]C1>CN(C=O)C>[CH2:27]([C:21]1[CH:20]=[C:19]([CH:24]=[CH:23][C:22]=1[CH2:25][CH3:26])[CH2:18][C@@H:2]([NH:1][C:49]([N:29]1[CH2:30][CH2:31][CH:32]([N:35]2[CH2:41][CH2:40][C:39]3[CH:42]=[CH:43][CH:44]=[CH:45][C:38]=3[NH:37][C:36]2=[O:46])[CH2:33][CH2:34]1)=[O:50])[C:3]([N:5]1[CH2:10][CH2:9][N:8]([CH:11]2[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]2)[CH2:7][CH2:6]1)=[O:4])[CH3:28]

Participants

5

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 113795873-(Piperidin-4-yl)-4,5-dihydro-1H-benzo[d][1,3]diazepin-2(3H)-oneHCID 11560098(R)-2-amino-3-(3,4-diethyl-phenyl)-1-[4-(1-methylpiperidin-4-yl)-piperazin-1-yl]-propan-1-one

Product 1

HCID 100322974-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylic acid-{(R)-1-(3,4-diethyl-benzyl)-2-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-2-oxo-ethyl}-amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1.70 g (4.39 mmol) of (R)-2-amino-3-(3,4-diethyl-phenyl)-1-[4-(1-methyl-piperidin-4-yl)-piperazin-1-yl]-propan-1-one, dissolved in 25 mL of THF, was slowly added dropwise to the ice-cooled mixture of 75 mL of THF and 0.80 g (4.63 mmol) of CDT. Then the mixture was stirred for 30 min in the ice bath and for a further 45 min at RT before the solution of 1.1 g (4.48 mmol) of 3-piperidin-4-yl-1,3,4,5-tetrahydro-1,3-benzodiazepin-2-one in 20 mL of DMF was added and refluxed for 4 h. The reaction mixture was evaporated down under reduced pressure, the residue was combined with 50 mL of 15% K2CO3 solution and exhaustively extracted with DCM. The combined organic extracts were washed with water, dried over MgSO4, evaporated down and purified through silica gel. The crystallisation was from acetone. The desired product was obtained in the form of a crystalline solid.

Workup

  1. temperaturecooled
  2. additionwas added
  3. temperaturerefluxed for 4 h
  4. customThe reaction mixture was evaporated down under reduced pressure
  5. extractionexhaustively extracted with DCM
  6. washThe combined organic extracts were washed with water
  7. dry with materialdried over MgSO4
  8. customevaporated down
  9. custompurified through silica gel
  10. customThe crystallisation

Sources & evidence

ORD record
ord-1937070e7af74c76b4ab5279198c542c
Source dataset
uspto-grants-2010_04
Patent number
US07700589B2

Reaction notes

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