1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 17-Cyclohexyl-18-[4-[2-morpholin-4-yl-5-(2-oxo-pyrrolidin-1-yl)-benzyloxy]-phenyl]-10,10-dioxo-10lambda6-thia-1,4,11-triaza-tricyclo[11.5.2.016,19]icosa-7,13(20),14,16(19),17-pentaene-3,12-dione

HRID 523316Notes

Reaction equation

HRID 523316 reaction equation
[CH2:1]([S:4]([NH2:7])(=[O:6])=[O:5])[CH:2]=[CH2:3].C(N=C=NCCCN(C)C)C.[CH2:19]([NH:23][C:24](=[O:76])[CH2:25][N:26]1[C:34]2[C:29](=[CH:30][CH:31]=[C:32]([C:35](NS(CC=C)(=O)=O)=[O:36])[CH:33]=2)[C:28]([CH:44]2[CH2:49][CH2:48][CH2:47][CH2:46][CH2:45]2)=[C:27]1[C:50]1[CH:55]=[CH:54][C:53]([O:56][CH2:57][C:58]2[CH:63]=[C:62]([N:64]3[CH2:68][CH2:67][CH2:66][C:65]3=[O:69])[CH:61]=[CH:60][C:59]=2[N:70]2[CH2:75][CH2:74][O:73][CH2:72][CH2:71]2)=[CH:52][CH:51]=1)[CH2:20]C=C>CN(C=O)C.CN(C)C1C=CN=CC=1.[Cl-].[Na+].O>[CH:44]1([C:28]2[C:29]3[CH:30]=[CH:31][C:32]4[C:35](=[O:36])[NH:7][S:4](=[O:6])(=[O:5])[CH2:1][CH:2]=[CH:3][CH2:20][CH2:19][NH:23][C:24](=[O:76])[CH2:25][N:26]([C:34]=3[CH:33]=4)[C:27]=2[C:50]2[CH:55]=[CH:54][C:53]([O:56][CH2:57][C:58]3[CH:63]=[C:62]([N:64]4[CH2:68][CH2:67][CH2:66][C:65]4=[O:69])[CH:61]=[CH:60][C:59]=3[N:70]3[CH2:71][CH2:72][O:73][CH2:74][CH2:75]3)=[CH:52][CH:51]=2)[CH2:49][CH2:48][CH2:47][CH2:46][CH2:45]1

Participants

7

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 14028213Prop-2-ene-1-sulfonamideHCID 59549037N-but-3-enyl-2-[3-cyclohexyl-2-[4-[2-morpholin-4-yl-5-(2-oxo-pyrrolidin-1-yl)-benzyloxy]-phenyl]-6-(prop-2-ene-1-sulfonylaminocarbonyl)-indol-1-yl]-acetamide

Product 1

HCID 6850844117-Cyclohexyl-18-[4-[2-morpholin-4-yl-5-(2-oxo-pyrrolidin-1-yl)-benzyloxy]-phenyl]-10,10-dioxo-10lambda6-thia-1,4,11-triaza-tricyclo[11.5.2.016,19]icosa-7,13(20),14,16(19),17-pentaene-3,12-dioneYield 87%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of intermediate 12-4 (438 mg, 0.622 mmol) and prop-2-ene-1-sulfon-amide (151 mg, 2 eq), synthesized as described in Journal of Enzyme Inhibition, 16(6), 475, 2001, in dry DMF (10 mL), were added 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDCI; 193 mg, 2 eq) and 4-dimethylaminopyridine (DMAP; 152 mg, 2 eq) at room temperature, under N2. After completion, the reaction mixture was poured into 200 mL of brine, and extracted with a mixture of ethyl acetate and THF (several times). The combined organic layers were dried over sodium sulfate, filtered and concentrated. The obtained residue was triturated in diethylether and filtered off to afford 436 mg (87% yield) of the desired product N-but-3-enyl-2-[3-cyclohexyl-2-[4-[2-morpholin-4-yl-5-(2-oxo-pyrrolidin-1-yl)-benzyloxy]-phenyl]-6-(prop-2-ene-1-sulfonylaminocarbonyl)-indol-1-yl]-acetamide 12-5 as an off-white solid; m/z=809 (M+H)+.

Workup

  1. extractionextracted with a mixture of ethyl acetate and THF (several times)
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe obtained residue was triturated in diethylether
  6. filtrationfiltered off

Sources & evidence

ORD record
ord-d2716385d56b43a1b2cf874176661e10
Source dataset
uspto-grants-2016_05
Patent number
US09334282B2

Reaction notes

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