Dimethylamine → 2-Dimethylamino-N-(3-{4-[3-methyl-4-(pyridin-3-yloxy)-phenylamino]-quinazolin-6-yl}-prop-2-ynyl)-acetamide

HRID 2180976Notes

Reaction equation

HRID 2180976 reaction equation
Cl[CH2:2][C:3]([NH:5][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][C:27]2[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=2)=[C:22]([CH3:33])[CH:21]=1)=[O:4].[CH3:34][NH:35][CH3:36].C1COCC1>CO>[CH3:34][N:35]([CH3:36])[CH2:2][C:3]([NH:5][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][C:27]2[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=2)=[C:22]([CH3:33])[CH:21]=1)=[O:4]

Participants

5

Reactant 3

HCID 674DimethylamineHCID 8028TetrahydrofuranHCID 224841242-Chloro-N-(3-{4-[3-methyl-4-(pyridin-3-yloxy)-phenylamino]-quinazolin-6-yl}-prop-2-ynyl)-acetamide

Product 1

HCID 101620532-Dimethylamino-N-(3-{4-[3-methyl-4-(pyridin-3-yloxy)-phenylamino]-quinazolin-6-yl}-prop-2-ynyl)-acetamideYield 99%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 2-Chloro-N-(3-{4-[3-methyl-4-(pyridin-3-yloxy)-phenylamino]-quinazolin-6-yl}-prop-2-ynyl)-acetamide (99 mg, 0.20 mmol) in MeOH (5 mL) was added a solution dimethylamine in THF (2 mL, 4.0 mmol). The resulting solution was refluxed under nitrogen for 1 hour. After concentration, the residue was further dried, dissolved in MeOH (1.0 mL), and treated with HCl gas for 3 minutes. The resulting solution was added to EtOAc with vigorous stirring to precipitate the HCl salt product as yellow solid which was collected by vacuum-filtration, rinsed with EtOAc, and further dried to give 110 mg (99%) of the title compound. 1H NMR (CD3OD) δ 2.30 (s, 3H), 2.96 (s, 6H), 4.03 (s, 2H), 4.37 (s, 2H), 7.27 (d, 1H), 7.72 (dt, 1H), 7.81(m, 1H), 7.84 (d, 1H), 8.03 (dd, 1H), 8.06 (d, 1H), 8.13 (dd, 1H), 8.59 (d, 1H), 8.68 (s, 1H), 8.81 (s, 1H), 8.84 (s, 1H); MS m/z (MH+) 467.3.

Workup

  1. temperatureThe resulting solution was refluxed under nitrogen for 1 hour
  2. concentrationAfter concentration
  3. dissolutiondissolved in MeOH (1.0 mL)
  4. additiontreated with HCl gas for 3 minutes
  5. additionThe resulting solution was added to EtOAc
  6. customto precipitate the HCl salt product as yellow solid which
  7. filtrationwas collected by vacuum-filtration
  8. washrinsed with EtOAc
  9. customfurther dried

Sources & evidence

ORD record
ord-4ffa6e642057407991f69617fe57da56
Source dataset
uspto-grants-2005_05
Patent number
US06890924B2

Reaction notes

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