Triethylamine → 3-(4-(4-(3-Fluorobenzyloxy)-3-chlorophenylamino)quinazolin-6-yl)prop-2-yn-1-ol

HRID 877090Notes

Reaction equation

HRID 877090 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][CH:28]=1)[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([NH:13][C:14]2[C:23]3[C:18](=[CH:19][CH:20]=[C:21](I)[CH:22]=3)[N:17]=[CH:16][N:15]=2)=[CH:9][C:8]=1[Cl:25].C[Si](C)(C)[O:31][CH2:32][C:33]#[CH:34].C(N(CC)CC)C>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>[F:1][C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][CH:28]=1)[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([NH:13][C:14]2[C:23]3[C:18](=[CH:19][CH:20]=[C:21]([C:34]#[C:33][CH2:32][OH:31])[CH:22]=3)[N:17]=[CH:16][N:15]=2)=[CH:9][C:8]=1[Cl:25]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 79696Silane, trimethyl(2-propyn-1-yloxy)-HCID 101745194-Quinazolinamine, N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-iodo-

Product 1

HCID 675042393-(4-(4-(3-Fluorobenzyloxy)-3-chlorophenylamino)quinazolin-6-yl)prop-2-yn-1-olYield 86%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of N-(4-(3-fluorobenzyloxy)-3-chlorophenyl)-6-iodoquinazolin-4-amine (1.52 g), trimethyl(prop-2-ynyloxy)silane (0.7 mL), triethyl amine (0.5 mL) in DMF (10 mL) was added Pd(PPh3)2Cl2 (106 mg), CuI (114 mg) and the mixture was heated at 40° C. overnight. The solvent was removed, then methanol (10 mL) and 4N HCl (2 mL) were added. The reaction mixture was stirred at room temperature for one hour and the solvent was removed. Another 10 mL methanol and triethyl amine (2 mL) were added and the reaction mixture was stirred at room temperature for one hour. The solvent was removed and the residue was purified by flash chromatography, eluting with EtOAc to give the desired product. LCMS ESI(+) m/z: 434 (M+1). Yield: 86%.

Workup

  1. customThe solvent was removed
  2. additionmethanol (10 mL) and 4N HCl (2 mL) were added
  3. customthe solvent was removed
  4. additionAnother 10 mL methanol and triethyl amine (2 mL) were added
  5. stirringthe reaction mixture was stirred at room temperature for one hour
  6. customThe solvent was removed
  7. customthe residue was purified by flash chromatography
  8. washeluting with EtOAc

Sources & evidence

ORD record
ord-08d7372c6d9a48b2a86288698731ddee
Source dataset
uspto-grants-2015_03
Patent number
US08987284B2

Reaction notes

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