Diisopropylethylamine → 6-(3-(2-(dimethylphosphinoyl)ethylamino)prop-1-ynyl)-N-(4-(3-fluorobenzyloxy)-3-chlorophenyl)quinazolin-4-amine

HRID 877092Notes

Reaction equation

HRID 877092 reaction equation
CS(O[CH2:6][C:7]#[C:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[N:15]=[CH:14][N:13]=[C:12]2[NH:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[CH:29]=2)=[C:22]([Cl:35])[CH:21]=1)(=O)=O.CCN(C(C)C)C(C)C.[CH3:45][P:46]([CH3:51])([CH2:48][CH2:49][NH2:50])=[O:47]>ClCCl>[CH3:45][P:46]([CH3:51])([CH2:48][CH2:49][NH:50][CH2:6][C:7]#[C:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[N:15]=[CH:14][N:13]=[C:12]2[NH:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[CH:29]=2)=[C:22]([Cl:35])[CH:21]=1)=[O:47]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 215271022-(Dimethylphosphinoyl)ethanamineHCID 866684763-(4-(4-(3-Fluorobenzyloxy)-3-chlorophenylamino)quinazolin-6-yl)prop-2-ynyl methanesulfonate2×

Product 1

HCID 498558666-(3-(2-(dimethylphosphinoyl)ethylamino)prop-1-ynyl)-N-(4-(3-fluorobenzyloxy)-3-chlorophenyl)quinazolin-4-amine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-(4-(4-(3-fluorobenzyloxy)-3-chlorophenylamino)quinazolin-6-yl)prop-2-ynyl methanesulfonate (compound 10.2, 319 mg), DIPEA (0.37 mL) in dichloromethane (20 mL) at 0° C. was added 2-(dimethylphosphinoyl)ethanamine (83 mg) and the reaction mixture was stirred at room temperature overnight. The solvent was removed and the residue was purified by flash chromatography, eluting with 20% methanol in dichloromethane to give the desired product as yellow solid. LCMS ESI(+) m/z: 538 (M+1). 1H NMR (300 MHz, CDCl3) δ 9.47 (s, 1H), 8.87 (s, 1H), 8.70 (s, 1H), 7.95 (m, 2H), 7.85 (m, 2H), 7.62 (m, 2H), 7.38 (m, 1H), 6.98 (m, 1H), 5.10 (s, 2H), 4.25 (m, 2H), 3.87 (m, 1H), 3.58 (m, 1H), 2.05 (m, 2H), 1.57 (m, 6H).

Workup

  1. customThe solvent was removed
  2. customthe residue was purified by flash chromatography
  3. washeluting with 20% methanol in dichloromethane

Sources & evidence

ORD record
ord-b11df927a3404a86be15b63a10aef862
Source dataset
uspto-grants-2015_03
Patent number
US08987284B2

Reaction notes

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