Lithium diisopropylamide → 5-(hydroxy(6-(trifluoromethyl)pyridin-3-yl)methyl)-1-methyl-6-(5-methylpyridin-3-yloxy)-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4 (1H,3H)-dione

HRID 60503Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 60503
[CH3:1][N:2]1[C:7]2[N:8]=[CH:9][C:10]([O:12][C:13]3[CH:14]=[N:15][CH:16]=[C:17]([CH3:19])[CH:18]=3)=[CH:11][C:6]=2[C:5](=[O:20])[N:4]([CH2:21][CH2:22][CH2:23][O:24][CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][O:26]2)[C:3]1=[O:31].[Li+].CC([N-]C(C)C)C.[F:40][C:41]([F:51])([F:50])[C:42]1[CH:49]=[CH:48][C:45]([CH:46]=[O:47])=[CH:44][N:43]=1>C1COCC1.CC(=O)OCC.O>[OH:47][CH:46]([C:45]1[CH:44]=[N:43][C:42]([C:41]([F:51])([F:40])[F:50])=[CH:49][CH:48]=1)[C:11]1[C:6]2[C:5](=[O:20])[N:4]([CH2:21][CH2:22][CH2:23][O:24][CH:25]3[CH2:30][CH2:29][CH2:28][CH2:27][O:26]3)[C:3](=[O:31])[N:2]([CH3:1])[C:7]=2[N:8]=[CH:9][C:10]=1[O:12][C:13]1[CH:14]=[N:15][CH:16]=[C:17]([CH3:19])[CH:18]=1

Komponenten

7

Edukt 3

HCID 2724682Lithium diisopropylamideHCID 27777626-(Trifluoromethyl)pyridine-3-carboxaldehydeHCID 1188755041-methyl-6-(5-methylpyridin-3-yloxy)-3-(3-(tetrahydro-2H-pyran-2-yloxy) propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione2×

Produkt 1

HCID 1188755185-(hydroxy(6-(trifluoromethyl)pyridin-3-yl)methyl)-1-methyl-6-(5-methylpyridin-3-yloxy)-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4 (1H,3H)-dioneAusbeute 12,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a solution of 1-methyl-6-(5-methylpyridin-3-yloxy)-3-(3-(tetrahydro-2H-pyran-2-yloxy) propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (See Compound 27, step 1, 140 mg, 0.330 mmol) in THF (10 mL) at −78° C. was added LDA (2M in THF, 0.84 mL, 1.65 mmol) dropwise The reaction was stirred at −78° C. for 1 h then a solution of 6-(trifluoromethyl) nicotinaldehyde (115 mg, 0.660 mmol) in THF (2 mL) was added. The reaction was stirred for 30 min at −78° C. then diluted with EA (10 mL) and water (10 mL). The organic layer was dried over Na2SO4 and concentrated to a residue which was purified by chromatography eluted with PE/EA (10:1 to 1:1) to give 5-(hydroxy(6-(trifluoromethyl)pyridin-3-yl)methyl)-1-methyl-6-(5-methylpyridin-3-yloxy)-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4 (1H,3H)-dione (24 mg, 12.1% yield) as a yellow oil. LCMS: [MH+-THP] 518 and TR=1.494 min.

Aufarbeitung

  1. stirringThe reaction was stirred for 30 min at −78° C.
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated to a residue which
  4. customwas purified by chromatography
  5. washeluted with PE/EA (10:1 to 1:1)

Quellen und Nachweise

ORD-Eintrag
ord-37c4da769843442894205b77bdb54ca4
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09440972B2

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