Diethyl Ether → 2-(3-([7-(3-chloropropoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)-N-(2,3-difluorophenyl)acetamide

HRID 749181Notes

Reaction equation

HRID 749181 reaction equation
[F:1][C:2]1[C:8]([F:9])=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].[Cl:10][CH2:11][CH2:12][CH2:13][O:14][C:15]1[CH:24]=[C:23]2[C:18]([C:19]([NH:25][C:26]3[CH:30]=[C:29]([CH2:31][C:32](O)=[O:33])[NH:28][N:27]=3)=[N:20][CH:21]=[N:22]2)=[CH:17][CH:16]=1.P(Cl)(Cl)(Cl)=O.CCOCC>N1C=CC=CC=1.C(OCC)(=O)C>[Cl:10][CH2:11][CH2:12][CH2:13][O:14][C:15]1[CH:24]=[C:23]2[C:18]([C:19]([NH:25][C:26]3[CH:30]=[C:29]([CH2:31][C:32]([NH:4][C:3]4[CH:5]=[CH:6][CH:7]=[C:8]([F:9])[C:2]=4[F:1])=[O:33])[NH:28][N:27]=3)=[N:20][CH:21]=[N:22]2)=[CH:17][CH:16]=1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 24813Phosphorus oxychloride2×HCID 782782,3-DifluoroanilineHCID 162214512-(5-((7-(3-Chloropropoxy)quinazolin-4-yl)amino)-1H-pyrazol-3-yl)acetic acid

Product 1

HCID 162214532-(3-([7-(3-chloropropoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)-N-(2,3-difluorophenyl)acetamideYield 89.3%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

2,3-difluoroaniline (1.15 g, 8.95 mmol) was added to a suspension of (3-{[7-(3-chloropropoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetic acid (2.70 g, 7.46 mmol) in pyridine (30 ml) and the reaction cooled to 0° C. Phosphorous oxychloride (1.14 g, 7.46 mmol) was added dropwise and the reaction stirred at 0° C. for 1 hour. The reaction was warmed to ambient temperature and more phosphorous oxychloride (0.5 ml) added. The reaction was stirred for 4.5 hours. The reaction mixture was diluted with ethyl acetate:ether (100 ml: 37 ml) and stirred for 18 hours. The precipitate was filtered, suspended in water and neutralised with ammonium hydroxide (7%, 15 ml). The resultant yellow suspension was filtered, washed with water and dried (phosphorous pentoxide) to yield 2-(3-{[7-(3-chloropropoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)-N-(2,3-difluorophenyl)acetamide as an orange powder (3.15 g, 89% yield):

Workup

  1. temperatureThe reaction was warmed to ambient temperature
  2. stirringThe reaction was stirred for 4.5 hours
  3. filtrationThe precipitate was filtered
  4. filtrationThe resultant yellow suspension was filtered
  5. washwashed with water
  6. dry with materialdried (phosphorous pentoxide)

Sources & evidence

ORD record
ord-a67375358cb1435c9f10ff05801a8c0f
Source dataset
uspto-grants-2008_07
Patent number
US07402585B2

Reaction notes

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