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

HRID 2055153Notes

Reaction equation

HRID 2055153 reaction equation
[Cl:1][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]2Cl)=[O:4].[CH3:20][C:21]1[CH:22]=[C:23]([NH2:34])[CH:24]=[CH:25][C:26]=1[O:27][C:28]1[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=1>CC(O)(C)C.ClCCCl>[Cl:1][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:34][C:23]1[CH:24]=[CH:25][C:26]([O:27][C:28]2[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=2)=[C:21]([CH3:20])[CH:22]=1)=[O:4]

Participants

4

Reactant 2

HCID 219252673-Methyl-4-(pyridin-3-yloxy)anilineHCID 224843152-Chloro-N-(3-(4-chloroquinazolin-6-yl)prop-2-yn-1-yl)acetamide

Product 1

HCID 224841242-Chloro-N-(3-{4-[3-methyl-4-(pyridin-3-yloxy)-phenylamino]-quinazolin-6-yl}-prop-2-ynyl)-acetamideYield 88.8%

Reagents, catalysts & solvents 1

HCID 21868497Tert-butyl alcohol 1,2-dichloroethaneSolvent

Procedure

A mixture of 2-Chloro-N-[3-(4-chloro-quinazolin-6-yl)-prop-2-ynyl]-acetamide (0.90 g, 3.05 mmol) and 3-Methyl-4-(pyridin-3-yloxy)-phenylamine (0.61 g, 3.05 mmol) in tBuOH/DCE (5.0/5.0 mL) was refluxed under nitrogen for 40 minutes and concentrated. The residue was dissolved in MeOH (2.0 mL) and added to EtOAc with vigorous stirring to precipitate the HCl salt product as tan solid which was collected by vacuum-filtration, rinsed with EtOAc, and further dried to give 1.24 g (82%) of 2-Chloro-N-(3-{4-[3-methyl-4-(pyridin-3-yloxy)-phenylamino]-quinazolin-6-yl}-prop-2-ynyl)-acetamide: 1H NMR (CD3OD) δ 2.27 (s, 3H), 4.09 (s, 2H), 4.29 (s, 2H), 7.07 (d, 1H), 7.51 (m, 2H), 7.60 (d, 1H), 7.70 (s, 1H), 7.78 (d, 1H), 8.05 (d, 1H), 8.32 (m, 2H), 8.67 (s, 1H), 8.75 (s, 1H); MS m/z (MH+) 458.0.

Workup

  1. temperaturewas refluxed under nitrogen for 40 minutes
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in MeOH (2.0 mL)
  4. additionadded to EtOAc
  5. customto precipitate the HCl salt product as tan solid which
  6. filtrationwas collected by vacuum-filtration
  7. washrinsed with EtOAc
  8. customfurther dried

Sources & evidence

ORD record
ord-9b56cfb7084249f8930cb5efbffe70c0
Source dataset
uspto-grants-2008_02
Patent number
US07332493B2

Reaction notes

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