Diisopropylethylamine → HCID 10178895, Verbindung

HRID 1432405Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1432405
[CH2:1]([NH:8][C:9]1[N:17]=[C:16](F)[N:15]=[C:14]2[C:10]=1[N:11]=[CH:12][N:13]2[CH:19]([CH3:21])[CH3:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH: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>[CH2:1]([NH:8][C:9]1[N:17]=[C:16]([NH:31][C@@H:32]([CH2:38][CH3:39])[CH:33]([OH:37])[CH:34]([CH3:36])[CH3:35])[N:15]=[C:14]2[C:10]=1[N:11]=[CH:12][N:13]2[CH:19]([CH3:21])[CH3:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 17954009Benzyl-(2-fluoro-9-isopropyl-9H-purin-6-yl)-amineHCID 57714157(3RS,4S)-4-Amino-2-methyl-hexan-3-ol

Produkt 1

HCID 10178895HCID 10178895, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 20476217n-BuOH DMSOLösungsmittel

Versuchsvorschrift

To a stirred solution of benzyl-(2-fluoro-9-isopropyl-9H-purin-6-yl)-amine (40 mg, 1 eq, 0.14 mmol) in n-BuOH/DMSO (2.5 mL, 4:1) at room temperature under an argon atmosphere was added DIEA (0.24 mL, 4.9 eq, 1.38 mmol) followed by (3RS,4S)-4-amino-2-methyl-hexan-3-ol (39 mg, 2.12 eq, 0.30 mmol). The reaction mixture-was placed in a preheated oil bath at 140° 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 (2×50 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 hexane:ether:MeOH (50:50:0→50:50:2) to afford the title compound as a white solid; Yield: 6.7 mg (12%). (50% de 45,3S: 50% de 4S,3R). 1H-NMR (d-CDCl3, 250 MHz): δ 0.95-1.04 (m, 9H, —NHCH(CH2CH3)CH(CH(CH3)2)OH), 1.57 (d, 6H, J=6.79 Hz, —CH(CH3)2), 1.62-1.88 (m, 4H, —NHCH(CH2CH3)CH(CH(CH3)2)OH), 3.26-3.32 (m, 1H, —NHCH(CH2CH3)CH(CH(CH3)2)OH), 3.87-4.00 (m, 1H, —NHCH(CH2CH3)CH(CH(CH3)2)OH), 4.57-4.70 (m, 1H, —CH(CH3)2), 4.76-4.90 (m, 2H, —HNCH2-Bz), 5.25-5.55 (m, 1H NHCH(CH2CH3)CH(CH(CH3)2)OH), 7.26-7.45 (m, 6H, 5×Bz-H+HNCH2-Bz), 7.53 (s, 1H, —N═CH—N). FABMS m/z (relative intensity): 397 ([M+H]+, 95), 385 (20), 323 (100). Accurate Mass (M+H): Actual: 397.2716, Measured: 393.2724.

Aufarbeitung

  1. customThe reaction mixture-was placed in a preheated oil bath at 140° 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 (2×50 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 hexane:ether:MeOH (50:50:0→50:50:2)

Quellen und Nachweise

ORD-Eintrag
ord-62cb23684cdd499e9b10d959da5a948b
Quelldatensatz
uspto-grants-2009_11
Patentnummer
US07612079B2

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