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Diisopropylethylamine → HCID 87122896, Verbindung

HRID 708704
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 708704
[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
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

7

Edukt 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

Produkt 1

HCID 87122896
HCID 87122896, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-4779975d45de4aa58e16fa7ad32d3009
Quelldatensatz
uspto-grants-2015_11
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09175003B2

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