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 39049노트

반응식

HRID 39049 반응식
[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

참가 물질

7

반응물 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

생성물 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-dione수율 87%

시약·촉매·용매 3

HCID 142844-(Dimethylamino)pyridine촉매HCID 6228Dimethylformamide용매HCID 57417360Sodium chloride; water용매

실험 절차

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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-83cf7e7cf22a48d4a6a34f37630bf8f0
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08524716B2

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