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

HRID 2207692Notes

Reaction equation

HRID 2207692 reaction equation
I[C:2]1[N:7]=[C:6]([CH3:8])[CH:5]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=2)[N:3]=1.[CH3:19][N:20]1[CH2:24][CH2:23][C@@:22]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])([CH2:25][C:26]#[CH:27])[C:21]1=[O:36].N(CC)CC>C1COCC1.[Cu](I)I>[CH3:19][N:20]1[CH2:24][CH2:23][C@@:22]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:32])([CH3:34])[CH3:33])([CH2:25][C:26]#[C:27][C:2]2[N:7]=[C:6]([CH3:8])[CH:5]=[C:4]([C:9]3[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=3)[N:3]=2)[C:21]1=[O:36]

Participants

6

Reactant 3

HCID 8021DiethylamineHCID 89649283tert-Butyl N-[(3S)-1-methyl-2-oxo-3-prop-2-ynyl-pyrrolidin-3-yl]carbamateHCID 90014635HCID 90014635, compound

Product 1

HCID 90014756tert-butyl N-[(3S)-1-methyl-3-[3-[4-methyl-6-[4-(trifluoromethyl)-phenyl]pyrimidin-2-yl]prop-2-ynyl]-2-oxo-pyrrolidin-3-yl]carbamateYield 106.7%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
20 °C

Procedure

Copper Iodide (149.46 mg, 0.7800 mmol), followed by PdCl2(Ph3P)2 (275.41 mg, 0.3900 mmol) was added portionwise to a solution of 2-iodo-4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidine (4 g, 10.99 mmol) (which may be prepared as described in Description 6), tert-butyl N-[(3S)-1-methyl-2-oxo-3-prop-2-ynyl-pyrrolidin-3-yl]carbamate (1.98 g, 7.85 mmol) (which may be prepared as described in Description 4) and Et2NH (4.06 mL, 39.24 mmol) in THF (50 mL) under N2 and the reaction was stirred at 20° C. for 18 hrs. The solvent was evaporated and the residue was suspended in EtOAc and washed with water/sat. aq. NaHCO3. The organics were collected, dried (Na2SO4) and the solvent evaporated to afford a brown oil. This was purified using a Biotage SP4, with a 100 g SNAP cartridge, eluting with 50 to 100% EtOAc/i-hexane to afford tert-butyl N-[(3S)-1-methyl-3-[3-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]prop-2-ynyl]-2-oxo-pyrrolidin-3-yl]carbamate (D7) (4.09 g, 8.3726 mmol) as a pale yellow foam;

Workup

  1. customThe solvent was evaporated
  2. washwashed with water/
  3. customThe organics were collected
  4. dry with materialdried (Na2SO4)
  5. customthe solvent evaporated
  6. customto afford a brown oil
  7. customThis was purified
  8. washwith a 100 g SNAP cartridge, eluting with 50 to 100% EtOAc/i-hexane

Sources & evidence

ORD record
ord-f05e64e863464c64af24b4471b5cf236
Source dataset
uspto-grants-2016_06
Patent number
US09376445B2

Reaction notes

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