Cyanogen Bromide → HCID 10343270, compound

HRID 1948902Notes

Reaction equation

HRID 1948902 reaction equation
[Cl:1][C:2]1[C:3]([F:29])=[C:4]([CH:26]=[CH:27][CH:28]=1)[NH:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:24][CH3:25])=[C:13]([O:16][CH2:17][CH:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)[CH:14]=2)[N:9]=[CH:8][N:7]=1.[CH:30]([N:33](C(C)C)CC)(C)C.N#CBr>C(Cl)Cl>[Cl:1][C:2]1[C:3]([F:29])=[C:4]([CH:26]=[CH:27][CH:28]=1)[NH:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:24][CH3:25])=[C:13]([O:16][CH2:17][CH:18]3[CH2:23][CH2:22][N:21]([C:30]#[N:33])[CH2:20][CH2:19]3)[CH:14]=2)[N:9]=[CH:8][N:7]=1

Participants

5

Reactant 3

HCID 10476Cyanogen BromideHCID 81531DiisopropylethylamineHCID 11742676HCID 11742676, compound

Product 1

HCID 10343270HCID 10343270, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-(3-Chloro-2-fluoroanilino)-7-methoxy-6-[(piperidin-4-yl)methoxy]quinazoline (Example 3, 104 mg, 0.25 mmol) was dissolved in DCM (10 ml), and diisopropylethylamine (4 μl, 0.28 mmol) was added. Cyanogen bromide solution (3M in DCM, 92 μl, 0.28 mmol) was added, and the solution stirred for 16 hours at ambient temperature. The solvent was evaporated, and the residue purified by chromatography, eluting with 0 to 2% (7:1 MeOH/concentrated aqueous NH4OH) in DCM. The appropriate fractions were combined and evaporated, and the residue triturated with diethyl ether to give the product as a white solid (75 mg, 68%); 1H NMR: 1.34-1.50 (m, 2H), 1.80-1.90 (m, 2H), 2.02 (m, 1H), 3.10 (m, 2H), 3.37-3.46 (m, 2H), 3.93 (s, 3H), 3.99 (d, 2H), 7.19 (s, 1H), 7.26 (dd, 1H), 7.46 (dd, 1H), 7.46 (dd, 1H), 7.50 (dd, 1H), 7.77 (s, 1H), 8.36 (s, 1H), 9.57 (s, 1H); Mass Spectrum: 442.4, 444.4.

Workup

  1. customThe solvent was evaporated
  2. customthe residue purified by chromatography
  3. washeluting with 0 to 2% (7:1 MeOH/concentrated aqueous NH4OH) in DCM
  4. customevaporated
  5. customthe residue triturated with diethyl ether

Sources & evidence

ORD record
ord-3d30aea461de44d8a2ebd26353fd70ff
Source dataset
uspto-grants-2013_03
Patent number
US08399667B2

Reaction notes

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