Diisopropylethylamine → (3RS,4S)-4-{9-Isopropyl-6-[(pyridin-2-ylmethyl)-amino]-9H-purin-2-ylamino}-2,2-dimethyl-hexan-3-ol

HRID 1984284Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1984284
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]([CH2:39][CH3:40])[CH:33]([OH:38])[C:34]([CH3:37])([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]([CH2:39][CH3:40])[CH:33]([OH:38])[C:34]([CH3:37])([CH3:36])[CH3:35])=[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 11565460(2-fluoro-9-isopropyl-9H-purin-6-yl)-pyridin-2-ylmethyl-amineHCID 57714146(3RS,4S)-4-amino-2,2-dimethyl-hexan-3-ol

Produkt 1

HCID 10001665(3RS,4S)-4-{9-Isopropyl-6-[(pyridin-2-ylmethyl)-amino]-9H-purin-2-ylamino}-2,2-dimethyl-hexan-3-ol

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 (5 mL, 4:1) at room temperature under an argon atmosphere was added DIEA (0.10 mL, 5.5 eq, 0.57 mmol) followed by (3RS,4S)-4-amino-2,2-dimethyl-hexan-3-ol (43 mg, 2.81 eq, 0.29 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 (2×25 mL), and the combined organic phase was washed with brine-(50 mL), dried,(NgSO4) 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: 5.9 mg (14%).(53% de 4S,3R: 47% de 4S,3S). 1H-NMR (d-CDCl3, 250 MHz): δ 1.00-1.04 (m, 12H, —NHCH(CH2CH3)CH(C(CH3OH), 1.56 & 1.58 (2×d, 6H, J=6.63 & 6.63 Hz, —CH(CH3)2), 1.67-1.90 (m, 2H, —NHCH(CH2CH3)CH(C(CH3)3)OH), 3.56 (d, 1H, J=1.89 Hz, —NHCH(CH2CH3)CH(C(CH3)3)OH), 3.70-3.83 (m, 1H, —NHCH(CH2CH3)CH (C(CH3)3) OH), 4.58-4.69 (m, 1H, —CH(CH3)2), 4.88-4.98 (m, 2H, —HNCH2-Pyr), 5.23-5.39 (m, 1H, —NHCH(CH2CH3)CH(C(CH3)3)OH), 6.71-6.80 (m, 1H, —HNCH2-Pyr), 7.17-7.24 (m, 1H, Pyr-H), 7.38 (d, 1H, J=7.90, Pyr-H), 7.57 (s, 1H, —N═CH—N—), 7.63-7.70 (m, 1H, Pyr-H), 8.61 (d, 1H, J=4.90 Hz, Pyr-H). FABMS m/z (relative intensity): 412 ([M+H]+, 100), 324 (75). Accurate Mass (M+H): Actual: 412.2825, Measured: 412.2835.

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 (2×25 mL)
  5. washthe combined organic phase was washed with brine-(50 mL)
  6. customdried,(NgSO4) and evaporated in vacuo
  7. customThe residue was purified by gradient column chromatography on silica gel
  8. washeluted with CHCl3:MeOH (100:0→98:2)

Quellen und Nachweise

ORD-Eintrag
ord-97b8580f3f504b3f942e138fc7d9d136
Quelldatensatz
uspto-grants-2009_06
Patentnummer
US07544689B2

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