Water → HCID 67297968, compound

HRID 1520391Notes

Reaction equation

HRID 1520391 reaction equation
[NH2:1][CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[C:13]3[C:18](=[CH:19][CH:20]=2)[N:17]=[C:16]([C:21]2[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=2)[N:15]=[C:14]3[NH:27][CH3:28])=[CH:7][CH:6]=1.C(N(CC)CC)C.[C:36](OC(=O)C)(=[O:38])[CH3:37].O>C(Cl)Cl>[CH3:28][NH:27][C:14]1[C:13]2[C:18](=[CH:19][CH:20]=[C:11]([C:8]3[CH:7]=[CH:6][C:5]([O:4][CH2:3][CH2:2][NH:1][C:36](=[O:38])[CH3:37])=[CH:10][CH:9]=3)[CH:12]=2)[N:17]=[C:16]([C:21]2[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=2)[N:15]=1

Participants

6

Reactant 4

HCID 962WaterHCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 67298130HCID 67298130, compound

Product 1

HCID 67297968HCID 67297968, compoundYield 60.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a 50 mL round-bottomed flask was added 6-(4-(2-aminoethoxy)phenyl)-N-methyl-2-(pyridin-3-yl)quinazolin-4-amine (15.0 mg, 0.040 mmol) and triethylamine (0.017 ml, 0.121 mmol) in CH2Cl2 (5 mL) to give a yellow solution. Acetic anhydride (4.58 μl, 0.048 mmol) was added and the mixture was stirred for 2 h at room temperature. Water (10 mL) was added to the mixture and extracted with ethyl acetate (2×10 mL). The organic layers were combined and washed with brine (1×20 mL), dried over Mg2SO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (eluted with CH2Cl2/MeOH 1:0 to 9:1). The product was converted to the HCl salt by addition of 4 M HCl-dioxane, then dissolved in a small amount of methanol, followed by ethyl acetate. The resulting solid was filtered and dried to give 10 mg of N-(2-(4-(4-(methylamino)-2-(pyridin-3-yl)quinazolin-6-yl)phenoxy)ethyl)acetamide as a HCl salt as a yellow solid in a 51% yield. LCMS m/z=414 (M+1) (Method C) (retention time=1.28 min). 1H NMR (300 MHz, DMSO) δ 10.26 (s, 1H), 9.62 (s, 1H), 9.06-8.90 (m, 2H), 8.81 (s, 1H), 8.34 (d, J=9.0 Hz, 1H), 8.17 (d, J=6.6 Hz, 2H), 7.86 (d, J=8.0 Hz, 3H), 7.13 (d, J=7.91 Hz, 2H), 4.06 (t, J=5.4 Hz, 2H), 3.52-3.38 (m, 2H), 3.30 (d, J=4.1 Hz, 3H), 1.84 (s, 3H).

Workup

  1. customto give a yellow solution
  2. extractionextracted with ethyl acetate (2×10 mL)
  3. washwashed with brine (1×20 mL)
  4. dry with materialdried over Mg2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography on silica gel (eluted with CH2Cl2/MeOH 1:0 to 9:1)
  8. additionThe product was converted to the HCl salt by addition of 4 M HCl-dioxane
  9. dissolutiondissolved in a small amount of methanol
  10. filtrationThe resulting solid was filtered
  11. customdried

Sources & evidence

ORD record
ord-90ced32fd695458e835ec2fa35feaf84
Source dataset
uspto-grants-2015_07
Patent number
US09073890B2

Reaction notes

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