Diisopropylethylamine → HCID 12111412, Verbindung

HRID 81449Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 81449
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:17]=[N:18][CH:19]=[CH:20][CH:21]=2)[N:3]=1.CCN(C(C)C)C(C)C.[NH2:31][C@@H:32]([CH2:38][CH3:39])[CH:33]([OH:37])[CH:34]([CH3:36])[CH3:35]>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]([CH2:38][CH3:39])[CH:33]([OH:37])[CH:34]([CH3:36])[CH3:35])=[N:3][C:4]=2[NH:14][CH2:15][C:16]1[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=1)([CH3:13])[CH3:12]

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 115220602-fluoro-9-isopropyl-N-(pyridin-3-ylmethyl)-9H-purin-6-amineHCID 57714157(3RS,4S)-4-Amino-2-methyl-hexan-3-ol

Produkt 1

HCID 12111412HCID 12111412, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 20476217n-BuOH DMSOLösungsmittel

Versuchsvorschrift

To a stirred solution of (2-fluoro-9-isopropyl-9H-purin-6-yl)-pyridin-3-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 (0.20 mL, 11 eq, 1.14 mmol) followed by (3RS,4S)-4-amino-2-methyl-hexan-3-ol (28 mg, 2.0 eq, 0.21 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 brine/water (1:1, 100 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: 4.3 mg (10%). 50% de 4S,3R: 50% de 4S,3S). 1H-NMR (d-CDCl3, 250 MHz): δ 0.91-1.05 (m, 9H, —NHCH(CH2CH3)CH(CH(CH3)2)OH), 1.57 (d, 6H, J=6.95 Hz, —CH(CH3)2), 1.60-1.95 (m, 4H, —NHCH(CH2CH3)CH(CH(CH3)2)OH), 3.23-3.33 (m, 1H, —NHCH(CH2CH3)CH(CH(CH3)2)OH), 3.84-4.04 (m, 1H, —NHCH(CH2CH3)CH(CH(CH3)2)OH), 4.56-4.70 (m, 1H, —CH(CH3)2), 4.77-4.95 (m, 2H, —HNCH2-Pyr), 5.26-5.43+6.27-6.50 (m, 1H, —NHCH(CH2CH3)CH(CH2CH3)OH), 7.23-7.37 (m, 3H, 2×Pyr-H & —N═CH—N—), 7.51-7.63 (m, 1H, Pyr-H), 7.73 (d, 1H, J=7.74 Hz, Pyr-H), 8.48-8.76 (m, 1H, HNCH2-Pyr). FABMS m/z (relative intensity): 398 ([M+H]+, 100), 324 (60). Accurate Mass (M+H): Actual: 398.2668, Measured: 398.2654.

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 brine/water (1:1, 100 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. dry with materialdried (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-0ede4e21a0eb40d9ac0d884ba9f4b5f3
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846696B2

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