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 626905Notes

Reaction equation

HRID 626905 reaction equation
[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]

Participants

7

Reactant 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

Product 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]carbamateYield 71.4%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 8028TetrahydrofuranSolventHCID 21882781Isohexane ethyl acetateSolvent

Conditions

Temperature
20 °C

Procedure

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.

Workup

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

Sources & evidence

ORD record
ord-f462cfdfce894280be1218790fdb2aae
Source dataset
uspto-grants-2016_04
Patent number
US09309254B2

Reaction notes

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