2-Methyl-3-butyn-2-ol → HCID 50915296, compound

HRID 1191322Notes

Reaction equation

HRID 1191322 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[C:6]([C:13]1[S:14][CH:15]=[CH:16][CH:17]=1)=[C:5]2[O:18][CH2:19][CH:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1.[CH3:26][C:27]([OH:31])([C:29]#[CH:30])[CH3:28].C(N(C(C)C)CC)(C)C>[Cu]I.[Pd].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>[O:23]1[CH2:24][CH2:25][CH:20]([CH2:19][O:18][C:5]2[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([C:30]#[C:29][C:27]([OH:31])([CH3:28])[CH3:26])[CH:3]=3)[NH:8][C:7](=[O:12])[C:6]=2[C:13]2[S:14][CH:15]=[CH:16][CH:17]=2)[CH2:21][CH2:22]1

Participants

6

Reactant 3

HCID 82582-Methyl-3-butyn-2-olHCID 81531DiisopropylethylamineHCID 50915293HCID 50915293, compound

Product 1

HCID 50915296HCID 50915296, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 2734558Bis(tri-tert-butylphosphine)palladium(0)Catalyst

Conditions

Temperature
100 °C

Procedure

A 5 mL microwave vial was charged with a magnetic stir bar, 6-bromo-4-(tetrahydro-2H-pyran-4-ylmethoxy)-3-(thiophen-2-yl)quinolin-2(1H)-one (22 mg, 52 mop, copper(I) iodide (1.0 mg, 5.0 mop, and bis(tri-t-butylphosphine) palladium(0) (1.0 mg, 3.0 μmol). The vessel was sealed. The contents of the vessel were dried under high vacuum, and flushed with nitrogen. Acetonitrile (500 μL) was added under nitrogen followed by addition of 2-methyl-3-butyn-2-ol (18 mg, 210 μmol), and diisopropylethyl amine (46 μL, 260 μmol). The reaction was heated to 100° C. in an oil bath for 3 h. The crude product was purified by reverse-phase chromatography to yield 4-(tetrahydro-2H-pyran-4-ylmethoxy)-6-(3-hydroxy-3-methylbut-1-yn-1-yl)-3-(thiophen-2-yl)quinolin-2(1H)-one as off white solid. LCMS (M+H)=423.9. 1H NMR (400 MHz, CDCl3) 11.0 (s, 1H), 7.90 (s, 1H), 7.84 (d, 1H), 7.52 (m, 2H), 7.24 (1H), 7.18 (t, 1H), 4.00 (dd, 2H) 3.65 (d, 2H), 3.45 (t, 2H), 2.15 (m, 1H), 1.75 (d, 2H), 1.65 (s, 6H), 1.50-1.40 (m, 3H).

Workup

  1. additionA 5 mL microwave vial was charged with a magnetic stir bar
  2. customThe vessel was sealed
  3. customThe contents of the vessel were dried under high vacuum
  4. customflushed with nitrogen
  5. additionAcetonitrile (500 μL) was added under nitrogen
  6. customThe crude product was purified by reverse-phase chromatography

Sources & evidence

ORD record
ord-6d35d5c768884dfb964a19e7ca74feac
Source dataset
uspto-grants-2014_03
Patent number
US08680116B2

Reaction notes

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