Diisopropylamine → (3-{4-[3-Chloro-4-(3-fluoro-benzyloxy)-phenylamino]-quinazolin-6-yl}-prop-2-ynyl)-carbamic acid tert-butyl ester

HRID 732271Notes

Reaction equation

HRID 732271 reaction equation
[C:1]([O:5][C:6](=[O:11])[NH:7][CH2:8][C:9]#[CH:10])([CH3:4])([CH3:3])[CH3:2].C(NC(C)C)(C)C.[Cl:19][C:20]1[CH:21]=[C:22]([NH:35][C:36]2[C:45]3[C:40](=[CH:41][CH:42]=[C:43](I)[CH:44]=3)[N:39]=[CH:38][N:37]=2)[CH:23]=[CH:24][C:25]=1[O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[CH:29]=1>C1COCC1.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>[C:1]([O:5][C:6](=[O:11])[NH:7][CH2:8][C:9]#[C:10][C:43]1[CH:44]=[C:45]2[C:40](=[CH:41][CH:42]=1)[N:39]=[CH:38][N:37]=[C:36]2[NH:35][C:22]1[CH:23]=[CH:24][C:25]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[CH:29]=2)=[C:20]([Cl:19])[CH:21]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 7912DiisopropylamineHCID 101745194-Quinazolinamine, N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-iodo-HCID 11073648tert-butyl N-(prop-2-yn-1-yl)carbamate

Product 1

HCID 66623753(3-{4-[3-Chloro-4-(3-fluoro-benzyloxy)-phenylamino]-quinazolin-6-yl}-prop-2-ynyl)-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

(3-{4-[3-Chloro-4-(3-fluoro-benzyloxy)-phenylamino]-quinazolin-6-yl}-prop-2-ynyl)-carbamic acid tert-butyl ester is prepared by adding prop-2-ynyl-carbamic acid tert-butyl ester (0.978 g, 6.31 mmol), diisopropylamine (1.77 ml, 12.63 mmol), Pd(PPh3)2Cl2 (210 mg, 0.30 mmol) and CuI (57 mg, 0.30 mmol) to a stirred solution of [3-chloro-4-(3-fluoro-benzyloxy)-phenyl]-(6-iodo-quinazolin-4-yl)-amine (3.11 g, 5.74 mmol) in THF (40 ml). After stirring the reaction mixture at rt under N2 for 3 h, the THF is removed under reduced pressured and methylene chloride is added. The organic layer is washed with NH4Cl (salt) and brine, and dried (Na2SO4). The solvent is evaporated and the residual solid is used without further purification.

Workup

  1. customthe THF is removed
  2. additionis added
  3. washThe organic layer is washed with NH4Cl (salt) and brine
  4. dry with materialdried (Na2SO4)
  5. customThe solvent is evaporated
  6. customthe residual solid is used without further purification

Sources & evidence

ORD record
ord-68a8924f69c34a8282935dbbd26c39f1
Source dataset
uspto-grants-2009_09
Patent number
US07585975B2

Reaction notes

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