Water → HCID 66610679, Verbindung

HRID 1621454

Reaktionsgleichung

Reaktionsgleichung von HRID 1621454
[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[CH:7]=[C:8]([C:13]2[N:21]=[C:20]([CH3:22])[N:19]=[C:18]3[C:14]=2[N:15]=[CH:16][N:17]3[CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][O:24]2)[C:9](F)=[N:10][CH:11]=1.[NH2:29][C:30]1[CH:31]=[CH:32][C:33]([O:36][CH3:37])=[N:34][CH:35]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.O>O1CCCC1>[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[CH:7]=[C:8]([C:13]2[N:21]=[C:20]([CH3:22])[N:19]=[C:18]3[C:14]=2[N:15]=[CH:16][N:17]3[CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][O:24]2)[C:9]([NH:29][C:30]2[CH:35]=[N:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=2)=[N:10][CH:11]=1

Komponenten

6

Edukt 4

HCID 962WaterHCID 811216-Methoxy-3-pyridinylamineHCID 2733832Lithium HexamethyldisilazideHCID 666114866-(5-(1,3-dioxolan-2-yl)-2-fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

Produkt 1

HCID 66610679HCID 66610679, VerbindungAusbeute 77,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

6-(5-(1,3-Dioxolan-2-yl)-2-fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (4.557 g, 11.82 mmol) and 5-amino-2-methoxypyridine (1.507 g, 12.14 mmol) were dissolved in tetrahydrofuran (80 mL) and cooled in an ice water bath. Then, LiHMDS (Aldrich 1.0 M in THF, 36.0 mL, 36.0 mmol) was added via syringe over about 10 minutes. The reaction was stirred under nitrogen at 0° C. for 40 minutes, and then the reaction was treated with water (100 mL) and warmed to room temperature. The layers were separated, and the aqueous phase was extracted with DCM. The aqueous phase was diluted with brine and extraction with DCM was continued. The combined organic extracts were combined, dried over sodium sulfate, filtered, concentrated, and purified on a silica gel filter (600 mL fritted filter, about 3 inches of silica gel, 80:1 DCM/2N ammonia in MeOH to 50:1 DCM/2N ammonia in MeOH) to give 5-(1,3-dioxolan-2-yl)-N-(6-methoxypyridin-3-yl)-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-amine (4.500 grams, 71% purity, 52% yield over two steps). MS MS (ESI pos. ion) m/z 446. Calculated exact mass for C23H23N7O3: 445 (M+—C2H4O). 1H NMR (CDCl3, 400 MHz) δ 12.69 (s, 1H), 9.91 (s, 1H), 8.44 (d, J=2.74 Hz, 1H), 8.41 (d, J=2.15 Hz, 1H), 8.29 (s, 1H), 8.23 (dd, J=8.80 Hz, 2.74 Hz, 1H), 6.79 (d, J=8.80 Hz, 1H), 5.94 (s, 1H), 5.87 (dd, J=10.56 Hz, 2.15 Hz, 1H), 4.24-4.17 (m, 3H), 4.12-4.05 (m, 2H), 3.96 (s, 3H), 3.88-3.79 (m, 1H), 2.91 (s, 3H), 2.19-2.00 (m, 3H), 1.93-1.77 (m, 3H).

Aufarbeitung

  1. temperaturecooled in an ice water bath
  2. temperaturewarmed to room temperature
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted with DCM
  5. additionThe aqueous phase was diluted with brine and extraction with DCM
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified on a silica gel
  10. filtrationfilter (600 mL fritted filter, about 3 inches of silica gel, 80:1 DCM/2N ammonia in MeOH to 50:1 DCM/2N ammonia in MeOH)

Quellen und Nachweise

ORD-Eintrag
ord-51bdc4887dbd4a53ad048904f0bf8ad9
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08772480B2

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