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Diisopropylethylamine → (5R,8S)-7-((S)-2-{(S)-2-Cyclohexyl-2-[((S)-1-isopropyl-piperidine-2-carbonyl)-amino]-acetylamino}-3,3-dimethyl-butyryl)-10,10-dimethyl-7-aza-dispiro[3.0.4.1]decane-8-carboxylic acid methyl ester

HRID 1502204
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1502204
[CH:1]([N:4]1[CH2:9][CH2:8][CH2:7][CH2:6][C@H:5]1[C:10]([OH:12])=O)([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:37][O:38][C:39]([C@@H:41]1[CH2:52][C@:44]2([C:49]([CH3:51])([CH3:50])[C:45]32[CH2:48][CH2:47][CH2:46]3)[CH2:43][N:42]1[C:53](=[O:70])[C@@H:54]([NH:59][C:60](=[O:69])[C@@H:61]([NH2:68])[CH:62]1[CH2:67][CH2:66][CH2:65][CH2:64][CH2:63]1)[C:55]([CH3:58])([CH3:57])[CH3:56])=[O:40].CCN(C(C)C)C(C)C>C(Cl)Cl>[CH3:37][O:38][C:39]([C@@H:41]1[CH2:52][C@:44]2([C:49]([CH3:50])([CH3:51])[C:45]32[CH2:48][CH2:47][CH2:46]3)[CH2:43][N:42]1[C:53](=[O:70])[C@@H:54]([NH:59][C:60](=[O:69])[C@H:61]([CH:62]1[CH2:63][CH2:64][CH2:65][CH2:66][CH2:67]1)[NH:68][C:10]([C@@H:5]1[CH2:6][CH2:7][CH2:8][CH2:9][N:4]1[CH:1]([CH3:2])[CH3:3])=[O:12])[C:55]([CH3:58])([CH3:57])[CH3:56])=[O:40]
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Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 49759876N-isopropyl-L-2-piperidinecarboxylic acidHCID 59533249(5R,8S)-7-[(S)-2-((S)-2-Amino-2-cyclohexyl-acetylamino)-3,3-dimethyl-butyryl]-10,10-dimethyl-7-aza-dispiro[3.0.4.1]decane-8-carboxylic acid methyl ester

Produkt 1

HCID 59533292
(5R,8S)-7-((S)-2-{(S)-2-Cyclohexyl-2-[((S)-1-isopropyl-piperidine-2-carbonyl)-amino]-acetylamino}-3,3-dimethyl-butyryl)-10,10-dimethyl-7-aza-dispiro[3.0.4.1]decane-8-carboxylic acid methyl ester

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A solution of (S)-1-isopropyl-piperidine-2-carboxylic acid (0.497 g; 2.90 mmol) and HATU (1.65 g; 4.35 mmol) in DCM (100 mL) was cooled to 0° C. and (5R,8S)-7-[(S)-2-((S)-2-Amino-2-cyclohexyl-acetylamino)-3,3-dimethyl-butyryl]-10,10-dimethyl-7-aza-dispiro[3.0.4.1]decane-8-carboxylic acid methyl ester (1.65 g; 2.90 mmol) and DIPEA (2.98 mL; 17.4 mmol) were added. The reaction mixture was stirred for 3 h at room temperature quenched with saturated aqueous bicarbonate. The aq. phase was extracted twice with DCM, the combined organic phases dried with Na2SO4, filtered and the solvent was removed in vacuo. The product was purified by preparative HPLC (method L) to yield the title compound. LC-MS (method E): Rt=1.62 min; M/z=629 [M+]; HPLC (method A3): Rt=5.01 min

Aufarbeitung

  1. customquenched with saturated aqueous bicarbonate
  2. extractionThe aq. phase was extracted twice with DCM
  3. dry with materialthe combined organic phases dried with Na2SO4
  4. filtrationfiltered
  5. customthe solvent was removed in vacuo
  6. customThe product was purified by preparative HPLC (method L)

Quellen und Nachweise

ORD-Eintrag
ord-c89adabfec8146739fc85dce0635f030
Quelldatensatz
uspto-grants-2015_12
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09206232B2

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