Dimethylformamide → HCID 58415364, compound

HRID 2075242Notes

Reaction equation

HRID 2075242 reaction equation
[CH2:1]([C:8]1[CH:9]=[C:10]([OH:16])[C:11](I)=[N:12][C:13]=1[Cl:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)C(C)C)C.[C:26]([C:28]1[CH:42]=[CH:41][C:31]([CH2:32][N:33]2[CH2:36][CH:35]([C:37]([O:39][CH3:40])=[O:38])[CH2:34]2)=[CH:30][C:29]=1[F:43])#[CH:27].CN(C=O)C>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>[CH2:1]([C:8]1[CH:9]=[C:10]2[O:16][C:26]([C:28]3[CH:42]=[CH:41][C:31]([CH2:32][N:33]4[CH2:36][CH:35]([C:37]([O:39][CH3:40])=[O:38])[CH2:34]4)=[CH:30][C:29]=3[F:43])=[CH:27][C:11]2=[N:12][C:13]=1[Cl:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 25254788Methyl 1-(4-ethynyl-3-fluorobenzyl)azetidine-3-carboxylateHCID 58415369HCID 58415369, compound

Product 1

HCID 58415364HCID 58415364, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalyst

Procedure

In a sealed flask was combined 5-benzyl-6-chloro-2-iodopyridin-3-ol (1.50 g, 4.3 mmol), PdCl2(PPh3)2 (0.30 g, 0.43 mmol), copper(I) iodide (0.17 g, 0.87 mmol), N-ethyl-N-isopropylpropan-2-amine (6.1 mL, 35 mmol), methyl 1-(4-ethynyl-3-fluorobenzyl)azetidine-3-carboxylate (1.2 g, 4.8 mmol) and DMF (10 mL, 129 mmol). The flask was flushed with argon, sealed and placed in an oil bath for 16 h at 80° C. The reaction was concentrated to remove solvent, and the resulting black mixture was adsorbed onto silica. Flash chromatography (100% EtOAc) afforded a yellow oil that was further purified on a Varian HF Mega Bond Elut SCX column (eluted with 2M ammonia in MeOH). Trituration with of the resulting solids with ether afforded an off-white solid. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 7.83-7.90 (1H, m), 7.49 (1H, s), 7.27-7.40 (5H, m), 7.22-7.24 (1H, m), 7.12-7.19 (2H, m), 4.20 (2H, s), 3.72 (3H, s), 3.65 (2H, s), 3.52-3.59 (2H, m), 3.32-3.38 (3H, m); MS (ESI) m/z: Calculated: 464.1; Observed: 465.1 (M++1).

Workup

  1. customIn a sealed flask was combined
  2. customThe flask was flushed with argon
  3. customsealed
  4. concentrationThe reaction was concentrated
  5. customto remove solvent
  6. customFlash chromatography (100% EtOAc) afforded a yellow oil that
  7. customwas further purified on a Varian HF Mega Bond Elut SCX column (eluted with 2M ammonia in MeOH)
  8. customTrituration with of the resulting solids with ether afforded an off-white solid

Sources & evidence

ORD record
ord-5412ca7880a74bea84e93251d7d8f123
Source dataset
uspto-grants-2011_04
Patent number
US07919519B2

Reaction notes

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