Diethylamine → tert-Butyl N-[(3S)-3-[3-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]prop-2-ynyl]-2-oxo-1-(2-trimethylsilylethoxymethyl)-3-piperidyl]carbamate

HRID 626905Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 626905
[CH2:1]([O:3][C:4]1[CH:5]=[CH:6][C:7]([F:18])=[C:8]([C:10]2[CH:15]=[C:14]([CH3:16])[N:13]=[C:12](I)[N:11]=2)[CH:9]=1)[CH3:2].[O:19]=[C:20]1[C@@:25]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])([CH2:26][C:27]#[CH:28])[CH2:24][CH2:23][CH2:22][N:21]1[CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42].N(CC)CC>C1COCC1.CCOC(C)=O.CCCC(C)C.[Cu](I)I>[CH2:1]([O:3][C:4]1[CH:5]=[CH:6][C:7]([F:18])=[C:8]([C:10]2[CH:15]=[C:14]([CH3:16])[N:13]=[C:12]([C:28]#[C:27][CH2:26][C@@:25]3([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:34])([CH3:33])[CH3:35])[CH2:24][CH2:23][CH2:22][N:21]([CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:43])([CH3:42])[CH3:44])[C:20]3=[O:19])[N:11]=2)[CH:9]=1)[CH3:2]

Komponenten

7

Edukt 3

HCID 8021DiethylamineHCID 900151884-(5-Ethoxy-2-fluoro-phenyl)-2-iodo-6-methyl-pyrimidineHCID 90016171tert-Butyl N-[(3S)-2-oxo-3-prop-2-ynyl-1-(2-trimethylsilylethoxymethyl)-3-piperidyl]carbamate

Produkt 1

HCID 90016260tert-Butyl N-[(3S)-3-[3-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]prop-2-ynyl]-2-oxo-1-(2-trimethylsilylethoxymethyl)-3-piperidyl]carbamateAusbeute 71,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 83717Copper iodideKatalysatorHCID 8028TetrahydrofuranLösungsmittelHCID 21882781Isohexane ethyl acetateLösungsmittel

Reaktionsbedingungen

Temperatur
20 °C

Versuchsvorschrift

Copper iodide (17.27 mg, 0.09 mmol), followed by PdCl2(Ph3P)2 (31.83 mg, 0.05 mmol) was added portionwise to a solution of 4-(5-ethoxy-2-fluoro-phenyl)-2-iodo-6-methyl-pyrimidine (which may be prepared as described in Description 17) (389.81 mg, 1.09 mmol), tert-butyl N-[(3S)-2-oxo-3-prop-2-ynyl-1-(2-trimethylsilylethoxymethyl)-3-piperidyl]carbamate (which may be prepared as described in D25) (347 mg, 0.9100 mmol) and Et2NH (0.47 mL, 4.54 mmol) in THF (10 mL) under N2 and the reaction was stirred at 20° C. for 90 hrs. The solvent was evaporated and the residue was purified using a Biotage SP4 with a 25 g SNAP cartridge, eluting with 0 to 50% EtOAc/i-hexane affording the tert-butyl N-[(3S)-3-[3-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]prop-2-ynyl]-2-oxo-1-(2-trimethylsilylethoxymethyl)-3-piperidyl]carbamate (D26) (397 mg, 0.6478 mmol, 71.4% yield) as a dark yellow oil.

Aufarbeitung

  1. customThe solvent was evaporated
  2. customthe residue was purified

Quellen und Nachweise

ORD-Eintrag
ord-f462cfdfce894280be1218790fdb2aae
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09309254B2

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