Pyridine → 2-Amino-6-(3-methoxy-1-propynyl)-N-(5-phenoxy-thiophen-2-ylmethyl)-nicotinamide

HRID 2080195Notes

Reaction equation

HRID 2080195 reaction equation
[NH2:1][C:2]1[N:23]=[C:22](Cl)[CH:21]=[CH:20][C:3]=1[C:4]([NH:6][CH2:7][C:8]1[S:9][C:10]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:11][CH:12]=1)=[O:5].C1C=CC(CC(NCN[C@H](C(O)=O)CC2C=CC([N+]([O-])=O)=CC=2)=O)=CC=1.[CH3:51][O:52][CH2:53][C:54]#[CH:55].C(N(C(C)C)CC)(C)C.N1C=CC=CC=1>C(#N)C.O.FC(F)(F)C(O)=O.[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.ClCCl.O.CN1CCCC1=O>[NH2:1][C:2]1[N:23]=[C:22]([C:55]#[C:54][CH2:53][O:52][CH3:51])[CH:21]=[CH:20][C:3]=1[C:4]([NH:6][CH2:7][C:8]1[S:9][C:10]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:11][CH:12]=1)=[O:5]

Participants

13

Reactant 5

HCID 1049PyridineHCID 693933-MethoxypropyneHCID 81531DiisopropylethylamineHCID 188218A-101HCID 231304982-aminochloro-N-(5-phenoxy-thiophen-2-ylmethyl)-nicotinamide

Product 1

HCID 231307162-Amino-6-(3-methoxy-1-propynyl)-N-(5-phenoxy-thiophen-2-ylmethyl)-nicotinamideYield 7.2%

Reagents, catalysts & solvents 7

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent2×HCID 13387N-methyl-2-pyrrolidoneSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
120 °C

Procedure

A mixture of 2-aminochloro-N-(5-phenoxy-thiophen-2-ylmethyl)-nicotinamide described in Example A-101 (15 mg, 0.042 mmol), methylpropargyl ether (3.5 mg, 0.050 mmol), diisopropylethylamine (0.023 mL, 0.13 mmol), pyridine (0.011 mL, 0.13 mmol), catalytic amount of copper(I) iodide, tetrakis(triphenylphosphine)palladium(0) (9.6 mg, 0.0083 mmol) and N-methylpyrrolidinone (1 mL) was stirred for 4 hours at 120° C. After cooling, water and dichloromethane were added to the reaction solution for extraction, and the organic layer was filtered through a membrane filter. The solvent was evaporated in vacuo, then, the residue was purified by reverse phase high performance liquid chromatography (acetonitrile-water mobile phase (containing 0.1% trifluoroacetic acid) was used), trifluoroacetic acid salt of the title compound (1.5 mg, 0.00030 mmol, 7.2%) was obtained.

Workup

  1. temperatureAfter cooling
  2. filtrationthe organic layer was filtered through a membrane
  3. filtrationfilter
  4. customThe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-806caaf96b844be3b281b09ab26682c0
Source dataset
uspto-grants-2011_04
Patent number
US07932272B2

Reaction notes

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