Diethylamine → tert-butyl N-[(3R)-3-[3-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]prop-2-ynyl]-1-methyl-2-oxo-pyrrolidin-3-yl]carbamate

HRID 626899Notes

Reaction equation

HRID 626899 reaction equation
[CH3:1][N:2]1[CH2:6][CH2:5][C@:4]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])([CH2:7][C:8]#[CH:9])[C:3]1=[O:18].[CH2:19]([O:21][C:22]1[CH:23]=[CH:24][C:25]([F:36])=[C:26]([C:28]2[CH:33]=[C:32]([CH3:34])[N:31]=[C:30](I)[N:29]=2)[CH:27]=1)[CH3:20].N(CC)CC>C1COCC1.CCOC(C)=O.CCCC(C)C.[Cu](I)I>[CH2:19]([O:21][C:22]1[CH:23]=[CH:24][C:25]([F:36])=[C:26]([C:28]2[CH:33]=[C:32]([CH3:34])[N:31]=[C:30]([C:9]#[C:8][CH2:7][C@@:4]3([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:15])([CH3:14])[CH3:16])[CH2:5][CH2:6][N:2]([CH3:1])[C:3]3=[O:18])[N:29]=2)[CH:27]=1)[CH3:20]

Participants

7

Reactant 3

HCID 8021DiethylamineHCID 900151884-(5-Ethoxy-2-fluoro-phenyl)-2-iodo-6-methyl-pyrimidineHCID 90015672tert-Butyl N-[(3R)-1-methyl-2-oxo-3-prop-2-ynyl-pyrrolidin-3-yl]carbamate

Product 1

HCID 90015138tert-butyl N-[(3R)-3-[3-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]prop-2-ynyl]-1-methyl-2-oxo-pyrrolidin-3-yl]carbamateYield 90.9%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 8028TetrahydrofuranSolventHCID 21882781Isohexane ethyl acetateSolvent

Conditions

Temperature
20 °C

Procedure

Copper iodide (26.27 mg, 0.14 mmol), followed by PdCl2(Ph3P)2 (48.41 mg, 0.07 mmol) was added portionwise to a solution of the tert-butyl N-[(3R)-1-methyl-2-oxo-3-prop-2-ynyl-pyrrolidin-3-yl]carbamate (which may be prepared as described in Description 10) (348 mg, 1.38 mmol), 4-(5-ethoxy-2-fluoro-phenyl)-2-iodo-6-methyl-pyrimidine (which may be prepared as described in D17) (642.17 mg, 1.79 mmol) and Et2NH (0.71 mL, 6.9 mmol) in THF (10 mL) under N2 and the reaction was stirred at 20° C. for 18 hrs. The solvent was evaporated and the residue was dissolved in EtOAc and washed with water. The organic layer was dried (Na2SO4) and the solvent was evaporated to afford an oil. This was purified on a Biotage SP4 using a 25 g SNAP cartridge, eluting with 50 to 100% EtOAc/i-hexane affording the tert-butyl N-[(3R)-3-[3-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]prop-2-ynyl]-1-methyl-2-oxo-pyrrolidin-3-yl]carbamate (D18) (605 mg, 1.2538 mmol, 90.9% yield) as a pale yellow foam.

Workup

  1. customThe solvent was evaporated
  2. dissolutionthe residue was dissolved in EtOAc
  3. washwashed with water
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. customthe solvent was evaporated
  6. customto afford an oil
  7. customThis was purified on a Biotage

Sources & evidence

ORD record
ord-77f06b83645d4068a9e8dcc4dd6fdcc2
Source dataset
uspto-grants-2016_04
Patent number
US09309254B2

Reaction notes

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