Dicyclohexylcarbodiimide → 2-(methylamino)-N-[6-(2-phenylethynyl)-4-(trifluoromethyl)pyridin-2-yl]propanamide

HRID 535429Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 535429
C[N:2]([C:8](OC(C)(C)C)=O)[CH:3]([CH3:7])[C:4]([OH:6])=O.C1(N=C=NC2CCCCC2)CCCCC1.[C:30]1([C:36]#[C:37][C:38]2[N:43]=[C:42]([NH2:44])[CH:41]=[C:40]([C:45]([F:48])([F:47])[F:46])[CH:39]=2)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.CCN(C(C)C)C(C)C>C(Cl)Cl.CN1C(=O)CCC1>[CH3:8][NH:2][CH:3]([CH3:7])[C:4]([NH:44][C:42]1[CH:41]=[C:40]([C:45]([F:47])([F:46])[F:48])[CH:39]=[C:38]([C:37]#[C:36][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[N:43]=1)=[O:6]

Komponenten

7

Edukt 4

HCID 10868DicyclohexylcarbodiimideHCID 81531DiisopropylethylamineHCID 44368572-(((Tert-butoxy)carbonyl)(methyl)amino)propanoic acidHCID 866944206-(2-Phenylethynyl)-4-(trifluoromethyl)pyridin-2-amine

Produkt 1

HCID 717149182-(methylamino)-N-[6-(2-phenylethynyl)-4-(trifluoromethyl)pyridin-2-yl]propanamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Versuchsvorschrift

A mixture of 2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]propanoic acid (620 mg, 3.05 mmol) and N,N′-dicyclohexylcarbodiimide (315 mg, 1.53 mmol) in DCM (4 ml) is stirred at RT for 30 minutes. This mixture is added to 6-(2-phenylethynyl)-4-(trifluoromethyl)pyridin-2-amine B3b (100 mg, 0.38 mmol) and DIPEA (73 μl; 0.42 mmol) in NMP (5 ml). After stirring for 6 days at 50° C. the reaction mixture is concentrated in vacuo and the boc-protected product purified by NP chromatography. The boc-protected product is treated with DCM:TFA (9:1, 4 ml) for 1.5 h at RT. This mixture is diluted with DCM and extracted with a saturated aqueous solution of NaHCO3. The combined organic layers are dried over MgSO4 and concentrated in vacuo. The product is purified by RP HPLC. Yield: 10.2 mg (8%). HPLC-MS: M+H=348; tR=1.46 (*Method—1).

Aufarbeitung

  1. stirringAfter stirring for 6 days at 50° C. the reaction mixture
  2. concentrationis concentrated in vacuo
  3. custompurified by NP chromatography
  4. additionThe boc-protected product is treated with DCM:TFA (9:1, 4 ml) for 1.5 h at RT
  5. additionThis mixture is diluted with DCM
  6. extractionextracted with a saturated aqueous solution of NaHCO3
  7. dry with materialThe combined organic layers are dried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customThe product is purified by RP HPLC

Quellen und Nachweise

ORD-Eintrag
ord-515122b4d2094f3b84f0b55beec6f044
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08859541B2

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