Diisopropylamine → (3-{4-[3-Methyl-4-(6-methyl-pyridin-3-yloxy)-phenylamino]-quinazolin-6-yl}-prop-2-ynyl)-carbamic acid tert-butyl ester

HRID 1725131Notes

Reaction equation

HRID 1725131 reaction equation
[C:1]([O:5][C:6](=[O:11])[NH:7][CH2:8][C:9]#[CH:10])([CH3:4])([CH3:3])[CH3:2].Cl.I[C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][CH:23]=1)[N:20]=[CH:19][N:18]=[C:17]2[NH:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][C:32]2[CH:33]=[N:34][C:35]([CH3:38])=[CH:36][CH:37]=2)=[C:27]([CH3:39])[CH:26]=1.C(NC(C)C)(C)C>C1COCC1.[Cu](I)I>[C:1]([O:5][C:6](=[O:11])[NH:7][CH2:8][C:9]#[C:10][C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][CH:23]=1)[N:20]=[CH:19][N:18]=[C:17]2[NH:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][C:32]2[CH:33]=[N:34][C:35]([CH3:38])=[CH:36][CH:37]=2)=[C:27]([CH3:39])[CH:26]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 7912DiisopropylamineHCID 11073648tert-butyl N-(prop-2-yn-1-yl)carbamateHCID 666233074-Quinazolinamine,6-iodo-n-[3-methyl-4-[(6-methyl-3-pyridinyl)oxy]phenyl]-,hydrochloride

Product 1

HCID 66623656(3-{4-[3-Methyl-4-(6-methyl-pyridin-3-yloxy)-phenylamino]-quinazolin-6-yl}-prop-2-ynyl)-carbamic acid tert-butyl esterYield 98%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of prop-2-ynyl-carbamic acid tert-butyl ester (2.65 g, 17.08 mmol) and (6-Iodo-quinazolin-4-yl)-[3-methyl-4-(6-methyl-pyridin-3-yloxy)-phenyl]-amine hydrochloride (8.2 g, 16.27 mmol), dichlorobis(triphenylphosphine) palladium (II) (570 mg, 0.81 mmol), copper iodide (154 mg, 0.81 mmol), and diisopropylamine (4.78 mL, 34.16 mmol) in anhydrous THF (80 mL) was stirred at room temperature for 5 hours. After concentration, the residue was dissolved in CH2Cl2 (100 mL), washed with aqueous NH4Cl and brine, dried over sodium sulfate, and concentrated to give the crude product (7.89 g, 98%) as a light yellow solid which was then used without further purification.

Workup

  1. concentrationAfter concentration
  2. dissolutionthe residue was dissolved in CH2Cl2 (100 mL)
  3. washwashed with aqueous NH4Cl and brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-7b0e188ab72444e0aa73e3afed79d0f7
Source dataset
uspto-grants-2009_02
Patent number
US07488823B2

Reaction notes

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