Triphenyl phosphite → HCID 178517777、化合物

HRID 473182ノート

反応式

HRID 473182 の反応式
[F:1][C:2]([F:13])([C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][N:7]=1)[C:3](O)=O.[NH2:14][C:15]1[C:23]([O:24][C:25]([F:28])([F:27])[F:26])=[CH:22][CH:21]=[CH:20][C:16]=1[C:17](O)=[O:18].P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1.Cl.[NH2:52]CCC(OCC)=O>N1C=CC=CC=1>[F:1][C:2]([F:13])([C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][N:7]=1)[C:3]1[N:52]=[C:17]([OH:18])[C:16]2[C:15](=[C:23]([O:24][C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][CH:20]=2)[N:14]=1

参加物

6

反応物 4

HCID 7540Triphenyl phosphiteHCID 458475beta-Alanine, ethyl ester, hydrochlorideHCID 117461722-amino-3-(trifluoromethoxy)benzoic AcidHCID 666095532,2-Difluoro-2-(5-fluoropyridin-2-yl)acetic acid

生成物 1

HCID 178517777HCID 178517777、化合物収率 77.2%

試薬・触媒・溶媒 1

HCID 1049Pyridine溶媒

反応条件

温度
150 °C

実験手順

To 2,2-difluoro-2-(5-fluoropyridin-2-yl)acetic acid from Example 33 step A (863 mg, 4.52 mmol) and 2-amino-3-(trifluoromethoxy)benzoic acid (1 g, 4.52 mmol) in pyridine (15 mL) was added triphenyl phosphite (1.3 mL, 4.97 mmol) and the mixture was heated in a microwave synthesizer at 150° C. for 10 min. The mixture was cooled to rt and then ethyl 3-aminopropanoate hydrochloride (763 mg, 4.97 mmol) was added and the mixture heated in a microwave synthesizer at 190° C. for 4 min. The crude mixture was concentrated under reduced pressure. THF (30 mL) was added followed by sodium ethoxide (21% in EtOH, 5 mL) and the mixture stirred at 60° C. for 0.5 h. The cooled mixture was concentrated under reduced pressure, dissolved in water and the pH adjusted to <4 by addition of 4 N HCl. The precipitate was collected by filtration, washed with water, and allowed to dry to afford 2-(difluoro(5-fluoropyridin-2-yl)methyl)-8-(trifluoromethoxy)quinazolin-4-ol (1.31 g, 77%) as a crude tan solid which was used in the next step without further purification.

後処理

  1. temperatureThe mixture was cooled to rt
  2. temperaturethe mixture heated in a microwave synthesizer at 190° C. for 4 min
  3. concentrationThe crude mixture was concentrated under reduced pressure
  4. additionTHF (30 mL) was added
  5. concentrationThe cooled mixture was concentrated under reduced pressure
  6. dissolutiondissolved in water
  7. additionthe pH adjusted to <4 by addition of 4 N HCl
  8. filtrationThe precipitate was collected by filtration
  9. washwashed with water
  10. customto dry

出典と根拠

ORDレコード
ord-50c95cc9623f4c5da9dd7948f0c04252
出典データセット
uspto-grants-2014_01
特許番号
US08633207B2

反応ノート

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