Triphenyl phosphite → HCID 178517777, 화합물

HRID 473182노트

반응식

HRID 473182 반응식
[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

참가 물질

6

반응물 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

생성물 1

HCID 178517777HCID 178517777, 화합물수율 77.2%

시약·촉매·용매 1

HCID 1049Pyridine용매

반응 조건

온도
150 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-50c95cc9623f4c5da9dd7948f0c04252
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08633207B2

반응 노트

불러오는 중…