Diethylamine → HCID 59596689, compound

HRID 2264829Notes

Reaction equation

HRID 2264829 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[F:16])=[CH:4][N:3]=1.[CH3:17][C:18]([O:21][C:22]([NH:24][C@@H:25]([CH2:30][C:31]#[CH:32])[C:26]([O:28][CH3:29])=[O:27])=[O:23])([CH3:20])[CH3:19].C(NCC)C>C(OCC)C.[Cu](I)I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:20][C:18]([O:21][C:22]([NH:24][C@@H:25]([CH2:30][C:31]#[C:32][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[F:16])=[CH:4][N:3]=1)[C:26]([O:28][CH3:29])=[O:27])=[O:23])([CH3:17])[CH3:19]

Participants

7

Reactant 3

HCID 8021DiethylamineHCID 11817013(S)-Methyl 2-((tert-butoxycarbonyl)amino)pent-4-ynoateHCID 59596668HCID 59596668, compound

Product 1

HCID 59596689HCID 59596689, compoundYield 40%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 3283Diethyl EtherSolvent

Procedure

To a solution of 2-bromo-5-{[(2-fluorophenyl)methyl]oxy}pyridine (D82, 0.60 g, 2.13 mmol), methyl (2S)-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-4-pentynoate (D64, 1.20 g, 5.30 mmol), synthesized with an analogous procedure to the one described hereinabove, and diethylamine (1.10 ml, 10.65 mmol) in diethyl ether (20 ml) were added copper iodide (0.042 g, 0.22 mmol) and PdCl2(PPh3)2 (0.077 g, 0.11 mmol) and the mixture was stirred for three hours at room temperature. The reaction was quenched with a saturated solution of ammonium chloride diluted with water and extracted with diethyl ether. The organic layer was dried (Na2SO4) filtered and evaporated. The residue was purified by chromatography on silica gel using cyclohexane/ethyl acetate (9:1 to 8:2) to afford the title compound as a yellow solid (0.36 g, 40%). Rt (HPLC): 5.64 min; MS: (ES/+) m/z: 429 [MH]+ C23H25FN2O5 requires 428; 1H NMR (400 MHz, CDCl3) δ (ppm): 8.28-8.39 (m, 1H); 7.44-7.53 (m, 1H); 7.32-7.41 (m, 2H); 7.16-7.25 (m, 2H); 7.08-7.16 (m, 1H); 5.37-5.55 (m, 1H); 5.19 (s, 2H); 4.46-4.66 (m, 1H); 3.81 (s, 3H); 2.91-3.07 (m, 2H); 1.47 (s, 9H).

Workup

  1. customThe reaction was quenched with a saturated solution of ammonium chloride
  2. additiondiluted with water
  3. extractionextracted with diethyl ether
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-742370fe5aa845d6be58d590a62bd5b1
Source dataset
uspto-grants-2010_12
Patent number
US07855218B2

Reaction notes

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