Triethylamine → HCID 86613615, compound

HRID 1907101Notes

Reaction equation

HRID 1907101 reaction equation
[CH2:1]([O:4][C@@H:5]1[C@@H:9]([CH2:10][OH:11])[O:8][C@@H:7]([N:12]2[CH:19]=[C:18](I)[C:16](=[O:17])[NH:15][C:13]2=[O:14])[CH2:6]1)[CH:2]=[CH2:3].C(N(CC)CC)C.[CH2:28]([NH:31][C:32](=[O:37])[C:33]([F:36])([F:35])[F:34])[C:29]#[CH:30]>CN(C=O)C.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([O:4][C@@H:5]1[C@@H:9]([CH2:10][OH:11])[O:8][C@@H:7]([N:12]2[CH:19]=[C:18]([C:30]#[C:29][CH2:28][NH:31][C:32](=[O:37])[C:33]([F:36])([F:35])[F:34])[C:16](=[O:17])[NH:15][C:13]2=[O:14])[CH2:6]1)[CH:2]=[CH2:3]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 110948052,2,2-trifluoro-N-(prop-2-yn-1-yl)acetamideHCID 67284230HCID 67284230, compound

Product 1

HCID 86613615HCID 86613615, compoundYield 95.4%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of (35) (400 mg, 1.0 mmol) in dry DMF (10 ml) was added CuI (38 mg, 20 μmol) and triethylamine (300 μl, 2.0 mmol). The propargyltrifluoroacetamide (453 mg, 3.0 mmol) was added drop wise, followed by Pd(PPh3)4 (110 mg, 9.5 μmol). The reaction was stirred for 16 h in the dark. The reaction was quenched by adding MeOH (10 ml), DCM (10 ml) and bicarbonate dowex. The mixture was stirred for 30 min and then filtered. The solvents were removed under vacuum and the crude product was purified by chromatography on silica (EtOAc: petrol 3:7 to 7:3). The product was isolated as slightly yellow crystals (398 mg, 95%). 1H NMR (d6 DMSO) δ 2.25-2.43 (m, 2H, H-2′), 3.65-3.76 (m, 2H, H-5′), 4.07-4.17 (m, 3H, H-4′, CH2), 4.21-4.23 (m, 1H, H-3′), 4.34 (d, J=5.5 Hz, 2H, CH2N), 5.25-5.27 (m, 2H, ═CH2, OH), 5.38 (dd, J=1.83, 17.3 Hz, 1H, ═CH2), 5.96-6.06 (m, 1H, ═CH), 6.17 (t, J=6.9 Hz, 1H, H-1′), 8.29 (s, 1H, H-6), 10.17 (t, J=5.5 Hz, 1H, NHTFA), 11.78 (s, 1H, NH). Mass (−ve electrospray) calcd for C17H18F3N3O6 417.11. Found 416.

Workup

  1. customThe reaction was quenched
  2. additionby adding MeOH (10 ml), DCM (10 ml) and bicarbonate dowex
  3. stirringThe mixture was stirred for 30 min
  4. filtrationfiltered
  5. customThe solvents were removed under vacuum
  6. customthe crude product was purified by chromatography on silica (EtOAc: petrol 3:7 to 7:3)

Sources & evidence

ORD record
ord-2f17aace41774b5bbf56fe8a7f9e6854
Source dataset
uspto-grants-2013_12
Patent number
US08597881B2

Reaction notes

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