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 626905노트

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HRID 626905 반응식
[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]

참가 물질

7

반응물 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

생성물 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]carbamate수율 71.4%

시약·촉매·용매 3

HCID 83717Copper iodide촉매HCID 8028Tetrahydrofuran용매HCID 21882781Isohexane ethyl acetate용매

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온도
20 °C

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-f462cfdfce894280be1218790fdb2aae
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09309254B2

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