4-Methylmorpholine → HCID 178427474, Verbindung

HRID 2365504Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2365504
[S:1]([NH:11][C@H:12]([C:20](O)=[O:21])[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2].CN1CCOCC1.Cl.Cl.[NH:32]1[C:36]2([CH2:41][CH2:40][NH:39][CH2:38][CH2:37]2)[CH2:35][NH:34]/[C:33]/1=[N:42]\[C:43]([C:45]1[C:50]([NH2:51])=[N:49][C:48]([NH2:52])=[C:47]([Cl:53])[N:46]=1)=[O:44].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[C:14]1([CH2:13][C@H:12]([NH:11][S:1]([C:4]2[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=2)(=[O:2])=[O:3])[C:20]([N:39]2[CH2:40][CH2:41][C:36]3([NH:32]/[C:33](=[N:42]/[C:43]([C:45]4[C:50]([NH2:51])=[N:49][C:48]([NH2:52])=[C:47]([Cl:53])[N:46]=4)=[O:44])/[NH:34][CH2:35]3)[CH2:37][CH2:38]2)=[O:21])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Komponenten

7

Edukt 4

HCID 79724-MethylmorpholineHCID 99327N-((4-Methylphenyl)sulfonyl)-L-phenylalanineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178478673HCID 178478673, Verbindung

Produkt 1

HCID 178427474HCID 178427474, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of Tosyl-L-phenylalanine (1.0 g, 3.13 mmol) in DMF (25 ml) is added N-methyl morpholine (1.033 ml, 9.39 mmol) and 3,5-Diamino-6-chloro-pyrazine-2-carboxylic acid [1,3,8-triaza-spiro[4.5]dec-(2E)-ylidene]-amide dihydrochloride (Ex. 38) (1.37 g, 3.44 mmol), followed by HATU (1.31 g, 3.44 mmol) and the resulting solution is stirred at room temperature for 20 minutes. The crude product is diluted with water (300 ml) and the resultant solid is isolated. Purification by reverse phase chromatography (Isolute™ C18, 0-100% MeCN in water −0.1% TFA) followed by catch and release resin (SCX-2) eluted with MeOH and 7M NH3 in MeOH yields a yellow solid which is triturated with MeOH and diethyl ether to give the title compound as a free base. The free base is stirred in 5M HCl at 100° C. for 30 minutes forming a gum. MeOH (5 ml) is added to the gum and then all solvent is removed in vacuo. The residue is triturated with MeOH and diethyl ether to give the title compound; [M+H]+ 626.4; 1H NMR (DMSO-d6): 1.12-1.71 (4H, m), 2.36-2.38 (3H, s), 2.59-2.83 (2H, m), 2.93-3.52 (4H, m), 3.41-3.60 (2H, m), 4.42 (1H, m), 7.12 (2H, d, J=6.9 Hz), 7.17-7.28 (3H, m), 7.35 (2H, d, J=7.7 Hz), 7.54-7.37 (2H, br), 7.57 (2H, d, J=7.7 Hz), 8.12 (1H, d, J=9.0 Hz), 7.70-8.26 (2H, br), 9.22 (1H, s), 9.95 (1H, s), 10.99 (1H, s).

Aufarbeitung

  1. customthe resultant solid is isolated
  2. customPurification by reverse phase chromatography (Isolute™ C18, 0-100% MeCN in water −0.1% TFA)
  3. washeluted with MeOH and 7M NH3 in MeOH
  4. customyields a yellow solid which
  5. customis triturated with MeOH and diethyl ether

Quellen und Nachweise

ORD-Eintrag
ord-553422b9f8164839b8ecf1862f99b26f
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08697687B2

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