Diethylene Glycol Monomethyl Ether → HCID 18753458, compound

HRID 547170Notes

Reaction equation

HRID 547170 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][CH2:7]O.C(P(CCCC)CCCC)CCC.[Cl:22][C:23]1[CH:42]=[CH:41][C:26]([NH:27][C:28]2[C:37]3[C:32](=[CH:33][C:34]([OH:40])=[C:35]([O:38][CH3:39])[CH:36]=3)[N:31]=[CH:30][N:29]=2)=[C:25]([F:43])[CH:24]=1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C(Cl)Cl.CCOCC>[ClH:22].[Cl:22][C:23]1[CH:42]=[CH:41][C:26]([NH:27][C:28]2[C:37]3[C:32](=[CH:33][C:34]([O:40][CH2:7][CH2:6][O:5][CH2:4][CH2:3][O:2][CH3:1])=[C:35]([O:38][CH3:39])[CH:36]=3)[N:31]=[CH:30][N:29]=2)=[C:25]([F:43])[CH:24]=1

Participants

7

Reactant 4

HCID 8134Diethylene Glycol Monomethyl EtherHCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 18753458HCID 18753458, compoundYield 88.7%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of 2-(2-methoxyethoxy)ethanol (90 mg, 0.75 mmol) in methylene chloride (1 ml) was added to tributylphosphine (320 mg, 1.58 mmol) and 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (200 mg, 0.63 mmol), (prepared as described for the starting material in Example 2), in methylene chloride (6 ml) at 0° C. under argon. To the resulting mixture 1,1′-(azodicarbonyl)dipiperidine (400 mg, 1.6 mmol) was added in portions. The mixture was allowed to warm to ambient temperature and stirred under argon for 2 hours. Ether (5 ml) was added, and the precipitated solids were removed by filtration. The volatiles were removed from the filtrate by evaporation, and the residue was purified by column chromatography eluting with methylene chloride/methanol (90/10). The resulting partially purified product was dissolved in acetone, and ethereal hydrogen chloride (0.6 ml of a 1M solution, 0.6 mmol) added. The resulting precipitated product was collected by filtration and dried to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(2-methoxyethoxy)ethoxy)quinazoline hydrochloride (128 mg, 44%).

Workup

  1. custom(prepared
  2. customat 0° C.
  3. customthe precipitated solids were removed by filtration
  4. customThe volatiles were removed from the filtrate by evaporation
  5. customthe residue was purified by column chromatography
  6. washeluting with methylene chloride/methanol (90/10)
  7. dissolutionThe resulting partially purified product was dissolved in acetone
  8. additionethereal hydrogen chloride (0.6 ml of a 1M solution, 0.6 mmol) added
  9. customThe resulting precipitated product
  10. filtrationwas collected by filtration
  11. customdried

Sources & evidence

ORD record
ord-e6469208ca85429c90126be67fbfe9cb
Source dataset
uspto-grants-2011_05
Patent number
USRE042353E1

Reaction notes

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