Diethylamine → tert-Butyl N-[(3S)-1-methyl-2-oxo-3-[3-[4-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]prop-2-ynyl]pyrrolidin-3-yl]carbamate

HRID 626880Notes

Reaction equation

HRID 626880 reaction equation
I[C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)[CH:5]=[CH:4][N:3]=1.[CH3:18][N:19]1[CH2:23][CH2:22][C@@:21]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])([CH2:24][C:25]#[CH:26])[C:20]1=[O:35].N(CC)CC>C1COCC1.CCOC(C)=O.O.[Cu](I)I>[CH3:18][N:19]1[CH2:23][CH2:22][C@@:21]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:31])([CH3:33])[CH3:32])([CH2:24][C:25]#[C:26][C:2]2[N:7]=[C:6]([C:8]3[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=3)[CH:5]=[CH:4][N:3]=2)[C:20]1=[O:35]

Participants

8

Reactant 3

HCID 8021DiethylamineHCID 89649283tert-Butyl N-[(3S)-1-methyl-2-oxo-3-prop-2-ynyl-pyrrolidin-3-yl]carbamateHCID 900151392-Iodo-4-[4-(trifluoromethyl)phenyl]pyrimidine

Product 1

HCID 90015348tert-Butyl N-[(3S)-1-methyl-2-oxo-3-[3-[4-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]prop-2-ynyl]pyrrolidin-3-yl]carbamateYield 87.3%

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
20 °C

Procedure

Copper iodide (25.51 mg, 0.1300 mmol), followed by PdCl2(Ph3P)2 (47.01 mg, 0.0700 mmol) was added portionwise to a solution of 2-iodo-4-[4-(trifluoromethyl)phenyl]pyrimidine (which may be prepared as described in Description 6) (703.46 mg, 2.01 mmol), tert-butyl N-[(3S)-1-methyl-2-oxo-3-prop-2-ynyl-pyrrolidin-3-yl]carbamate (which may be prepared as described in D4) (338 mg, 1.34 mmol) and Et2NH (0.69 mL, 6.7 mmol) in THF (10 mL) under N2 and the reaction was stirred at 20° C. for 18 hrs. The reaction was diluted with EtOAc and water was added. The phases were separated and the organic layer was dried (Na2SO4) and the solvent evaporated to afford a brown oil. This was purified by using a Biotage SP4, with a 25 g SNAP cartridge, eluting with 0 to 100% EtOAc in i-hexane to afford tert-butyl N-[(3S)-1-methyl-2-oxo-3-[3-[4-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]prop-2-ynyl]pyrrolidin-3-yl]carbamate (D7) (555 mg, 1.17 mmol, 87.3% yield) as a yellow oil.

Workup

  1. additionwas added
  2. customThe phases were separated
  3. dry with materialthe organic layer was dried (Na2SO4)
  4. customthe solvent evaporated
  5. customto afford a brown oil
  6. customThis was purified
  7. washwith a 25 g SNAP cartridge, eluting with 0 to 100% EtOAc in i-hexane

Sources & evidence

ORD record
ord-39a01eab1d944a53809930220691306b
Source dataset
uspto-grants-2016_04
Patent number
US09309254B2

Reaction notes

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