Methylamine → 2-(ethylamino)-N-[5-pyrimidin-5-yl-6-(2-quinolin-6-ylethynyl)pyridin-2-yl]butanamide

HRID 535423Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 535423
[N:1]1[CH:6]=[C:5]([C:7]2[CH:8]=[CH:9][C:10]([NH2:25])=[N:11][C:12]=2[C:13]#[C:14][C:15]2[CH:16]=[C:17]3[C:22](=[CH:23][CH:24]=2)[N:21]=[CH:20][CH:19]=[CH:18]3)[CH:4]=[N:3][CH:2]=1.[CH3:26][CH2:27][N:28](C(C)C)C(C)C.Br[CH:36]([CH2:40][CH3:41])[C:37](Br)=[O:38].CN>C(Cl)Cl.C1COCC1.CN1C(=O)CCC1>[CH2:27]([NH:28][CH:36]([CH2:40][CH3:41])[C:37]([NH:25][C:10]1[CH:9]=[CH:8][C:7]([C:5]2[CH:6]=[N:1][CH:2]=[N:3][CH:4]=2)=[C:12]([C:13]#[C:14][C:15]2[CH:16]=[C:17]3[C:22](=[CH:23][CH:24]=2)[N:21]=[CH:20][CH:19]=[CH:18]3)[N:11]=1)=[O:38])[CH3:26]

Komponenten

8

Edukt 4

HCID 6329MethylamineHCID 81531DiisopropylethylamineHCID 1172932-Bromobutanoyl bromideHCID 866944135-Pyrimidin-5-yl-6-(2-quinolin-6-ylethynyl)pyridin-2-amine

Produkt 1

HCID 866944122-(ethylamino)-N-[5-pyrimidin-5-yl-6-(2-quinolin-6-ylethynyl)pyridin-2-yl]butanamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6344DichloromethaneLösungsmittel2×HCID 8028TetrahydrofuranLösungsmittelHCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Versuchsvorschrift

5-pyrimidin-5-yl-6-(2-quinolin-6-ylethynyl)pyridin-2-amine G2b (600 mg, 1.86 mmol) is mixed with NMP (10 ml) and DIPEA (1.42 ml, 8.35 mmol). 2-Bromobutanoyl bromide (985 μl, 8.17 mmol) is added dropwise. The mixture stirred for 1 h at RT. The 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 crude intermediate is mixed with a THF solution of methylamine (2 mol/l, 5 ml, 10 mmol) and stirred at RT for 16 h. The 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: 250 mg (32%). HPLC-MS: M+H=423; tR=1.25 min (*Method—1).

Aufarbeitung

  1. extractionextracted with a saturated aqueous solution of NaHCO3
  2. dry with materialThe combined organic layers are dried over MgSO4
  3. concentrationconcentrated in vacuo
  4. stirringstirred at RT for 16 h
  5. extractionextracted with a saturated aqueous solution of NaHCO3
  6. dry with materialThe combined organic layers are dried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe product is purified by RP HPLC

Quellen und Nachweise

ORD-Eintrag
ord-c2813ae979d3436c916f4e26cc601651
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08859541B2

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