Diisopropylethylamine → 4-{(S)-2-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-4-oxo-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butyryl}-piperazin-1-sulphonic acid (1-methyl-piperidin-4-yl)-amide

HRID 736943Notes

Reaction equation

HRID 736943 reaction equation
[NH2:1][C:2]1[C:33]([C:34]([F:37])([F:36])[F:35])=[CH:32][C:5]([CH2:6][C@@H:7]([CH2:11][C:12](=[O:31])[N:13]2[CH2:18][CH2:17][CH:16]([N:19]3[CH2:25][CH2:24][C:23]4[CH:26]=[CH:27][CH:28]=[CH:29][C:22]=4[NH:21][C:20]3=[O:30])[CH2:15][CH2:14]2)[C:8](O)=[O:9])=[CH:4][C:3]=1[Cl:38].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.[CH3:70][N:71]1[CH2:76][CH2:75][CH:74]([NH:77][S:78]([N:81]2[CH2:86][CH2:85][NH:84][CH2:83][CH2:82]2)(=[O:80])=[O:79])[CH2:73][CH2:72]1>C1COCC1.CCOC(C)=O.CN(C=O)C>[CH3:70][N:71]1[CH2:76][CH2:75][CH:74]([NH:77][S:78]([N:81]2[CH2:86][CH2:85][N:84]([C:8](=[O:9])[C@@H:7]([CH2:6][C:5]3[CH:32]=[C:33]([C:34]([F:36])([F:37])[F:35])[C:2]([NH2:1])=[C:3]([Cl:38])[CH:4]=3)[CH2:11][C:12](=[O:31])[N:13]3[CH2:18][CH2:17][CH:16]([N:19]4[CH2:25][CH2:24][C:23]5[CH:26]=[CH:27][CH:28]=[CH:29][C:22]=5[NH:21][C:20]4=[O:30])[CH2:15][CH2:14]3)[CH2:83][CH2:82]2)(=[O:80])=[O:79])[CH2:73][CH2:72]1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 43373695Piperazin-1-sulphonic acid-(1-methyl-piperidin-4-yl)-amideHCID 68591515(S)-2-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-4-oxo-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butanoic acid

Product 1

HCID 578484434-{(S)-2-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-4-oxo-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butyryl}-piperazin-1-sulphonic acid (1-methyl-piperidin-4-yl)-amide

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 500 mg (0.90 mmol) (S)-2-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-4-oxo-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butanoic acid and 320 mg (1.00 mmol) TBTU in 0.2 mL (1.14 mmol) ethyldiisopropylamine and 50 mL THF was stirred for 1 h at RT. Then 270 mg (1.03 mmol) piperazin-1-sulphonic acid-(1-methyl-piperidin-4-yl)-amide and 5 mL DMF were added. The reaction solution was stirred overnight at RT. The reaction mixture was diluted with 50 mL EtOAc, extracted with 30 mL 15% K2CO3 solution and the organic phase was dried over Na2SO4. After the desiccant and solvent had been eliminated the residue was purified by chromatography (silica gel, gradient: DCM to DCM/MeOH/NH3 10:9:1).

Workup

  1. extractionextracted with 30 mL 15% K2CO3 solution
  2. dry with materialthe organic phase was dried over Na2SO4
  3. customwas purified by chromatography (silica gel, gradient: DCM to DCM/MeOH/NH3 10:9:1)

Sources & evidence

ORD record
ord-31025908faed43c39ec64942fc9d837a
Source dataset
uspto-grants-2009_09
Patent number
US07595312B2

Reaction notes

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