Lithium Hexamethyldisilazide → 5-(3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-ylamino)-6-methylisoquinolin-1(2H)-one

HRID 1042268

Reaktionsgleichung

Reaktionsgleichung von HRID 1042268
F[C:2]1[C:7]([C:8]2[C:9]3[CH:16]=[CH:15][NH:14][C:10]=3[N:11]=[CH:12][N:13]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[NH2:17][C:18]1[C:27]([CH3:28])=[CH:26][CH:25]=[C:24]2[C:19]=1[CH:20]=[CH:21][NH:22][C:23]2=[O:29].C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[N:11]1[C:10]2[NH:14][CH:15]=[CH:16][C:9]=2[C:8]([C:7]2[C:2]([NH:17][C:18]3[C:27]([CH3:28])=[CH:26][CH:25]=[C:24]4[C:19]=3[CH:20]=[CH:21][NH:22][C:23]4=[O:29])=[N:3][CH:4]=[CH:5][CH:6]=2)=[N:13][CH:12]=1

Komponenten

5

Edukt 3

HCID 2733832Lithium HexamethyldisilazideHCID 529879275-amino-6-methylisoquinolin-1(2H)-oneHCID 596273704-(2-fluoropyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine

Produkt 1

HCID 596273715-(3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-ylamino)-6-methylisoquinolin-1(2H)-oneAusbeute 69,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A mixture of 4-(2-fluoropyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine (463 mg, 2162 μmol) and 5-amino-6-methylisoquinolin-1(2H)-one (377 mg, 2162 μmol) in THF (1.5 mL) was sonicated for 5 min until all the solid was mixed well. Lithium bis(trimethylsilyl)amide (9.7 mL, 9.72 mmol; 1 M in THF) was added via a syringe and the reaction tube was sonicated and stirred at RT for 5 min. The reaction was heated to 120° C. in a microwave for 20 min. The reaction mixture was cooled to rt and partitioned between DCM and NaHCO3. The aqueous layer was washed with DCM three times. The combined organic layers were washed with brine and dried over Na2SO4, then concentrated in vacuo. The residue was purified via flash column on silica (MeOH-DCM=0.5-6%) to give a light brown solid 5-(3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-ylamino)-6-methylisoquinolin-1(2H)-one (550 mg, 69% yield). MS (ESI, pos. ion) m/z: 369

Aufarbeitung

  1. customwas sonicated for 5 min until all the solid
  2. additionwas mixed well
  3. customthe reaction tube was sonicated
  4. temperatureThe reaction was heated to 120° C. in a microwave for 20 min
  5. temperatureThe reaction mixture was cooled to rt
  6. custompartitioned between DCM and NaHCO3
  7. washThe aqueous layer was washed with DCM three times
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified via flash column on silica (MeOH-DCM=0.5-6%)

Quellen und Nachweise

ORD-Eintrag
ord-4539f2471f5d41a8a54f045e1a80adb6
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08557830B2

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