2-Bromoacetamide → HCID 10411907, compound

HRID 1948899Notes

Reaction equation

HRID 1948899 reaction equation
[Cl:1][C:2]1[C:3]([F:28])=[C:4]([CH:25]=[CH:26][CH:27]=1)[NH:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:23][CH3:24])=[C:13]([O:16][CH:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)[CH:14]=2)[N:9]=[CH:8][N:7]=1.C(N(C(C)C)CC)(C)C.Br[CH2:39][C:40]([NH2:42])=[O:41]>C(Cl)Cl>[C:40]([CH2:39][N:20]1[CH2:21][CH2:22][CH:17]([O:16][C:13]2[CH:14]=[C:15]3[C:10](=[CH:11][C:12]=2[O:23][CH3:24])[N:9]=[CH:8][N:7]=[C:6]3[NH:5][C:4]2[CH:25]=[CH:26][CH:27]=[C:2]([Cl:1])[C:3]=2[F:28])[CH2:18][CH2:19]1)(=[O:41])[NH2:42]

Participants

5

Reactant 3

HCID 696322-BromoacetamideHCID 81531DiisopropylethylamineHCID 10408840N-(3-chloro-2-fluorophenyl)-7-methoxy-6-(piperidin-4-yloxy)quinazolin-4-amine

Product 1

HCID 10411907HCID 10411907, compoundYield 61.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-(3-Chloro-2-fluoroanilino)-7-methoxy-6-[(piperidin-4-yl)oxy]quinazoline (Example 2, 70 mg, 0.17 mmol) was dissolved in DCM (10 ml), and diisopropylethylamine (45 μl, 0.26 mmol) was added. 2-Bromoacetamide (36 mg, 0.26 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 3% (7:1 MeOH/concentrated aqueous NH4OH) in DCM. The appropriate fractions were combined and evaporated, and the residue crystallised from acetonitrile to give the product as a white crystalline solid (48 mg, 60%); 1H NMR: 1.70-1.84 (m, 2H), 1.98-2.09 (m, 2H), 2.38 (m, 2H), 2.70-2.80 (m, 2H), 2.89 (s, 2H), 3.92 (s, 3H), 4.54 (m, 1H), 7.08 (br. s, 2H), 7.20 (s, 1H), 7.26 (ddd, 1H), 7.47 (ddd, 1H), 7.51 (ddd, 1H), 7.80 (s, 1H), 8.35 (s, 1H), 9.53 (s, 1H); Mass Spectrum: 460.5, 462.4.

Workup

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

Sources & evidence

ORD record
ord-2620058cd6f74cd1b768722d81b38cc2
Source dataset
uspto-grants-2013_03
Patent number
US08399667B2

Reaction notes

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