Chloroacetonitrile → HCID 9980764, compound

HRID 1948900Notes

Reaction equation

HRID 1948900 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(=O)([O-])[O-].[K+].[K+].Cl[CH2:36][C:37]#[N:38]>CC(N(C)C)=O>[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][N:20]([CH2:36][C:37]#[N:38])[CH2:19][CH2:18]3)[CH:14]=2)[N:9]=[CH:8][N:7]=1

Participants

5

Reactant 3

HCID 7856ChloroacetonitrileHCID 11430Potassium CarbonateHCID 10408840N-(3-chloro-2-fluorophenyl)-7-methoxy-6-(piperidin-4-yloxy)quinazolin-4-amine

Product 1

HCID 9980764HCID 9980764, compoundYield 37.3%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
60 °C

Procedure

4-(3-Chloro-2-fluoroanilino)-7-methoxy-6-[(piperidin-4-yl)oxy]quinazoline (Example 2, 70 mg, 0.17 mmol) was dissolved in DMA (5 ml). Potassium carbonate (96 mg, 0.70 mmol) and chloroacetonitrile (17 μl, 0.25 mmol) were added. The mixture was stirred at 60° C. for 4 hours. The solvent was evaporated and the residue was partitioned between DCM (20 ml) and water (20 ml). The aqueous layer was extracted with DCM (2×10 ml) and the extractions combined with the DCM layer. The combined DCM fractions were filtered through a silicone-treated filter paper and evaporated. The residue was 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, giving the product as a white solid (28 mg, 36%); 1H NMR: 1.67-1.80 (m, 2H), 2.03-2.13 (m, 2H), 2.46 (m, 2H), 2.77-2.85 (m, 2H), 3.76 (s, 2H), 3.92 (s, 3H), 4.55 (m, 1H), 7.20 (s, 1H), 7.27 (dd, 1H), 7.47 (dd, 1H), 7.52 (dd, 1H), 7.80 (s, 1H), 8.35 (s, 1H), 9.54 (s, 1H); Mass Spectrum: 412.4, 444.4.

Workup

  1. customThe solvent was evaporated
  2. customthe residue was partitioned between DCM (20 ml) and water (20 ml)
  3. extractionThe aqueous layer was extracted with DCM (2×10 ml)
  4. extractionthe extractions
  5. filtrationThe combined DCM fractions were filtered through a silicone-
  6. additiontreated
  7. filtrationfilter paper
  8. customevaporated
  9. customThe residue was purified by chromatography
  10. washeluting with 0 to 2% (7:1 MeOH/concentrated aqueous NH4OH) in DCM
  11. customevaporated
  12. customthe residue triturated with diethyl ether

Sources & evidence

ORD record
ord-a6524a517d764f18a6861f61f9ddb4a6
Source dataset
uspto-grants-2013_03
Patent number
US08399667B2

Reaction notes

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