Diisopropylethylamine → HCID 12111406, Verbindung

HRID 1984278Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1984278
F[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]([CH3:13])[CH3:12])=[C:4]([NH:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)[N:3]=1.CCN(C(C)C)C(C)C.[NH2:31][C@H:32]([CH2:36][CH3:37])[C@@H:33]([OH:35])[CH3:34]>CCCCO.CS(C)=O>[CH:11]([N:8]1[CH:7]=[N:6][C:5]2[C:9]1=[N:10][C:2]([NH:31][C@H:32]([CH2:36][CH3:37])[C@@H:33]([OH:35])[CH3:34])=[N:3][C:4]=2[NH:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=1)([CH3:13])[CH3:12]

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 10866272(2S,3R)-3-aminopentan-2-olHCID 11565460(2-fluoro-9-isopropyl-9H-purin-6-yl)-pyridin-2-ylmethyl-amine

Produkt 1

HCID 12111406HCID 12111406, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 20476217n-BuOH DMSOLösungsmittel

Versuchsvorschrift

To a stirred solution of (2-fluoro-9-isopropyl-9H-purin-6-yl)-pyridin-2-ylmethyl-amine (30 mg, 1 eq, 0.10 mmol) in n-BuOH/DMSO (2.5 mL, 4:1) at room temperature under an argon atmosphere was added DIEA (0.2 mL, 10.96 eq, 1.14 mmol) followed by (2S,3R)-3-amino-pentan-2-ol (60 mg, 5.5 eq, 0.58 mmol). The reaction mixture was placed in a preheated oil bath at 160° C. and stirred at this temperature for 72 h. The reaction mixture was allowed to cool to room temperature and the solvent was evaporated in vacuo. The residue was partitioned between EtOAc (50 mL) and water (50 mL), the aqueous phase was extracted with more EtOAc (2×25 mL), and the combined organic phase was washed with brine (50 mL), dried (MgSo4) and evaporated in vacuo. The residue was purified by gradient column chromatography on silica gel eluted with CHCl3:MeOH (100:0→98:2), to afford the title compound as a white solid. Yield: 36.1 mg (93%). (80% de 3R,2S: 20% de 3R,2R). 1H-NMR (d-CDCl3, 250 MHz): δ 0.91 & 1.06 (2×t, 3H, J=7.11 & 7.42 Hz, —NHCH(CH2CH3)CH(CH3)OH), 1.16 & 1.29 (2×d, 3H, J=6.48 & 3.48 Hz, —NHCH (CH2CH3)CH3)OH) 1.57 (d, 6H, J=6.79 Hz, —CH(CH3)2), 1.71-2.01 (m, 2H, —NHCH(CH2CH3)CH(CH3)OH), 3.98 (m, 2H, —NHCH(CH2CH3)CH(CH3)OH), 4.58-4.69 (m, 1H, —CH(CH3)2), 4.83-5.00 (m, 2H, —HNCH2-Pyr), 6.75-6.91 (m, 1H, —HNCH2-Pyr), 7.19-7.25 (m, 1H, Pyr-H), 7.37 (d, 1H, J=8.05 Hz, Pyr-H), 7.57 (s, 1H, —N═CH—N), 7.64-7.71 (m, 1H, Pyr-H), 8.61 (d, 1H, J=4.58 Hz, Pyr-H). FABMS m/z (relative intensity): 370 ([M+H]+, 100), 324 (40). Accurate Mass (M+H): Actual: 370.2355, Measured: 370.2347.

Aufarbeitung

  1. customThe reaction mixture was placed in a preheated oil bath at 160° C.
  2. customthe solvent was evaporated in vacuo
  3. customThe residue was partitioned between EtOAc (50 mL) and water (50 mL)
  4. extractionthe aqueous phase was extracted with more EtOAc (2×25 mL)
  5. washthe combined organic phase was washed with brine (50 mL)
  6. customdried (MgSo4)
  7. customevaporated in vacuo
  8. customThe residue was purified by gradient column chromatography on silica gel
  9. washeluted with CHCl3:MeOH (100:0→98:2)

Quellen und Nachweise

ORD-Eintrag
ord-2e445a70e6fa4472908df95ec7dbd9db
Quelldatensatz
uspto-grants-2009_06
Patentnummer
US07544689B2

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