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Diisopropylethylamine → HCID 87122896, 화합물

HRID 708704
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HRID 708704 반응식
[C:1]([O:5][C:6]([NH:8][C:9]1[S:10][C:11]([C:15]([OH:17])=O)=[C:12]([CH3:14])[N:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(F)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:33][O:34][C:35](=[O:85])[C@@H:36]([NH:52][C:53]([CH:55]1[CH2:64][C:63]2[CH:62]=[C:61]3[O:65][CH2:66][C@H:67]([C:69]4[CH:74]=[CH:73][C:72]([O:75][CH2:76][C:77]5[CH:82]=[CH:81][C:80]([Cl:83])=[C:79]([Cl:84])[CH:78]=5)=[CH:71][CH:70]=4)[O:68][C:60]3=[CH:59][C:58]=2[CH2:57][NH:56]1)=[O:54])[CH2:37][C:38]1[CH:43]=[CH:42][C:41]([C:44]2[CH:49]=[CH:48][C:47]([C:50]#[N:51])=[CH:46][CH:45]=2)=[CH:40][CH:39]=1.CCN(C(C)C)C(C)C>C1COCC1.CCOC(C)=O>[CH3:33][O:34][C:35](=[O:85])[C@@H:36]([NH:52][C:53]([CH:55]1[CH2:64][C:63]2[CH:62]=[C:61]3[O:65][CH2:66][C@H:67]([C:69]4[CH:74]=[CH:73][C:72]([O:75][CH2:76][C:77]5[CH:82]=[CH:81][C:80]([Cl:83])=[C:79]([Cl:84])[CH:78]=5)=[CH:71][CH:70]=4)[O:68][C:60]3=[CH:59][C:58]=2[CH2:57][N:56]1[C:15]([C:11]1[S:10][C:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[N:13][C:12]=1[CH3:14])=[O:17])=[O:54])[CH2:37][C:38]1[CH:43]=[CH:42][C:41]([C:44]2[CH:45]=[CH:46][C:47]([C:50]#[N:51])=[CH:48][CH:49]=2)=[CH:40][CH:39]=1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 2756770N-Boc-amino-4-methylthiazole-5-carboxylic acidHCID 2774761Tetramethylfluoroformamidinium hexafluorophosphateHCID 66719338(S)-3-(4'-cyano-biphenyl-4-yl)-2-({(S)-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl}-amino)-propionic acid methyl ester

생성물 1

HCID 87122896
HCID 87122896, 화합물

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

2-tert-Butoxycarbonylamino-4-methyl-thiazole-5-carboxylic acid (1 eq) and TFFH (1 eq) were taken in 2 mL anhydrous THF and stirred for 10 min. (S)-3-(4′-Cyano-biphenyl-4-yl)-2-({(S)-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl}-amino)-propionic acid methyl ester (50 mg) and DIEA (3 eq) were added to the reaction mixture and stirred for 1 hour. Reaction mixture was diluted with EtOAc (5 mL), washed with water and brine and dried over Na2SO4. The solvent was removed by rotavap and the residue was purified by silicagel column to give (S)-2-({(S)-7-(2-tert-butoxycarbonylamino-4-methyl-thiazole-5-carbonyl)-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl}-amino)-3-(4′-cyano-biphenyl-4-yl)-propionic acid methyl ester (42 mg). Treatment with HCl according to General Procedure C followed by NaHCO3 wash gave (S)-2-({(S)-7-(2-Amino-4-methyl-thiazole-5-carbonyl)-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl}-amino)-3-(4′-cyano-biphenyl-4-yl)-propionic acid methyl ester (35 mg).

후처리

  1. additionwere added to the reaction mixture
  2. customReaction mixture
  3. washwashed with water and brine
  4. dry with materialdried over Na2SO4
  5. customThe solvent was removed by rotavap
  6. customthe residue was purified by silicagel column

출처 및 근거

ORD 기록
ord-4779975d45de4aa58e16fa7ad32d3009
출처 데이터셋
uspto-grants-2015_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09175003B2

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