Triethylamine → HCID 18396231, compound

HRID 611562Notes

Reaction equation

HRID 611562 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([OH:9])[C:5](I)=[N:6][CH:7]=1.C(N(CC)CC)C.[C:17]([N:24]1[CH2:28][CH2:27][CH2:26][C@H:25]1[C:29]#[CH:30])([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18]>CN(C=O)C.CCOCC.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.[Cu]I>[C:17]([N:24]1[CH2:28][CH2:27][CH2:26][C@H:25]1[C:29]1[O:9][C:4]2[C:5](=[N:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)[CH:30]=1)([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18]

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 11030701(S)-N-Boc-2-ethynylpyrrolidineHCID 227146035-Chloro-2-iodopyridin-3-ol

Product 1

HCID 18396231HCID 18396231, compound

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×

Procedure

A 5.63 g (22.0 mmol) sample of 5-chloro-2-iodo-3-pyridinol, from step 7a above, was dissolved in 10 mL of DMF, and (Ph3P)2PdCl2 (0.38 g, 0.50 mmol), CuI (0.377 g, 1.98 mmol) and triethylamine (1.90 mL, 13.6 mmol) were added. The mixture was stirred under N2 at room temperature for 1 hour, then 2.15 g (11.0 mmol) of 1-BOC-2-(S)-ethynylpyrrolidine, from Example 1c above, dissolved in 5 mL of DMF, was added carefully. The reaction was stirred at 60° C. for 16 hours, then cooled to room temperature. The reaction mixture was diluted with ether, then washed with 10% NaOH and brine, then dried over MgSO4. The solvent was removed, and the residue was chromatographed on silica gel, eluting with 100:0 to 60:40 hexane:EtOAc to give 2.04 g of title compound: 1H NMR (CDCl3, 300 MHz) δ 1.3, 1.45 (2 s, 9H), 1.94-2.3 (m, 4H), 3.45-3.65 (m, 2H), 4.97-5.1 (m, 1H). 6.66 (s, 1H), 7.70 (s, 1H), 8.47 (s, 1H); MS m/z: 323 (M+H)+.

Workup

  1. additionwas added carefully
  2. stirringThe reaction was stirred at 60° C. for 16 hours
  3. temperaturecooled to room temperature
  4. washwashed with 10% NaOH and brine
  5. dry with materialdried over MgSO4
  6. customThe solvent was removed
  7. customthe residue was chromatographed on silica gel
  8. washeluting with 100:0 to 60:40 hexane

Sources & evidence

ORD record
ord-f4cf39cb38c949439fa59edaa7bb9e3c
Source dataset
uspto-grants-1999_12
Patent number
US06001849

Reaction notes

Loading…