Ammonium Chloride → 4-[1-(2-aminopyrimidin-4-yl)-2-ethoxy-1H-1,3-benzodiazol-6-yl]-2-(pyrimidin-2-yl)but-3-yn-2-ol

HRID 1398647Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1398647
[CH2:1]([O:3][C:4]1[N:8]([C:9]2[CH:14]=[CH:13][N:12]=[C:11]([NH2:15])[N:10]=2)[C:7]2[CH:16]=[C:17]([C:20]#[CH:21])[CH:18]=[CH:19][C:6]=2[N:5]=1)[CH3:2].C([N-]C(C)C)(C)C.[Li+].[N:30]1[CH:35]=[CH:34][CH:33]=[N:32][C:31]=1[C:36](=[O:38])[CH3:37].[Cl-].[NH4+]>C1COCC1>[NH2:15][C:11]1[N:10]=[C:9]([N:8]2[C:7]3[CH:16]=[C:17]([C:20]#[C:21][C:36]([C:31]4[N:32]=[CH:33][CH:34]=[CH:35][N:30]=4)([OH:38])[CH3:37])[CH:18]=[CH:19][C:6]=3[N:5]=[C:4]2[O:3][CH2:1][CH3:2])[CH:14]=[CH:13][N:12]=1

Komponenten

6

Edukt 4

HCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamideHCID 116079091-(Pyrimidin-2-yl)ethan-1-oneHCID 866696064-(2-ethoxy-6-ethynyl-1H-1,3-benzodiazol-1-yl)pyrimidin-2-amine

Produkt 1

HCID 681817934-[1-(2-aminopyrimidin-4-yl)-2-ethoxy-1H-1,3-benzodiazol-6-yl]-2-(pyrimidin-2-yl)but-3-yn-2-ol

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a solution of 4-(2-ethoxy-6-ethynyl-1H-1,3-benzodiazol-1-yl)pyrimidin-2-amine (110 mg, 0.37 mmol) in dry THF (1 mL) at −78° C. was introduced lithium diisopropylamide (0.47 mL of a 2M solution in THF, 0.935 mmol). After 5 minutes, 1-pyrimidin-2-yl-ethanone (81 mg, 0.65 mmol) was added and the reaction mixture maintained at −78° C. for 20 minutes. Following 30 minutes at RT, saturated aqueous ammonium chloride (0.5 ml) was added and the solution concentrated in vacuo. The residue was dissolved in DCM (10 mL), washed with water (2 mL), dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by column chromatography (Biotage, DCM containing a 0-8% gradient of methanol) furnished the title compound as a beige solid: 1H NMR (500 MHz, DMSO) delta 1.44 (3H, t, J=7.09 Hz), 1.88 (3H, s), 4.63 (2H, q, J=7.09 Hz), 6.14 (1H, s), 6.96 (1H, d, J=5.36 Hz), 7.09 (2H, br.s.), 7.22 (1H, dd, J=8.20, 1.58 Hz), 7.43 (1H, d, J=8.20 Hz), 7.49 (1H, t, J=4.81 Hz), 8.10 (1H, d, J=1.10 Hz), 8.38 (1H, d, J=5.36 Hz), 8.88 (2H, d, J=4.89 Hz); LC-MS: m/z=+402.45 (M+H)+.

Aufarbeitung

  1. waitFollowing 30 minutes at RT
  2. concentrationthe solution concentrated in vacuo
  3. dissolutionThe residue was dissolved in DCM (10 mL)
  4. washwashed with water (2 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification of the residue by column chromatography (Biotage, DCM containing a 0-8% gradient of methanol)

Quellen und Nachweise

ORD-Eintrag
ord-1158f5845ea14b739ade1c379ebb5a52
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901313B2

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