Triphenyl phosphite → HCID 178488826、化合物

HRID 473202

反応式

HRID 473202 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][CH3:25])=[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.[NH2:49]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:49]=[C:17]([OH:18])[C:16]2[C:15](=[C:23]([O:24][CH3:25])[CH:22]=[CH:21][CH:20]=2)[N:14]=1

参加物

6

反応物 4

HCID 7540Triphenyl phosphiteHCID 2557202-Amino-3-methoxybenzoic acidHCID 458475beta-Alanine, ethyl ester, hydrochlorideHCID 666095532,2-Difluoro-2-(5-fluoropyridin-2-yl)acetic acid

生成物 1

HCID 178488826HCID 178488826、化合物収率 71%

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 (1 g, 5.23 mmol) and 2-amino-3-methoxybenzoic acid (875 mg, 5.23 mmol) in pyridine (15 mL) was added triphenyl phosphite (1.51 mL, 5.75 mmol) and the mixture was heated in a microwave synthesizer at 150° C. for 10 min. The mixture was allowed to cool to rt and then ethyl 3-aminopropanoate hydrochloride (883 mg, 5.75 mmol) was added. The mixture was heated in a microwave synthesizer at 190° C. for 4 min and then concentrated under reduced pressure. THF (10 mL) and sodium ethoxide (21% in EtOH, 4 mL) were added, and the mixture was stirred at 60° C. for 0.5 h. The mixture was allowed to cool and concentrated under reduced pressure. The residue was dissolved in water and the pH was adjusted to <4 by addition of 4 N HCl. The precipitate was collected by filtration, washed with water, and dried on the funnel to afford 2-(difluoro(5-fluoropyridin-2-yl)methyl)-8-methoxyquinazolin-4-ol (1.19 g, 71%). LC-MS (ESI) m/z 322 (M+H)+.

後処理

  1. temperatureto cool to rt
  2. temperatureThe mixture was heated in a microwave synthesizer at 190° C. for 4 min
  3. concentrationconcentrated under reduced pressure
  4. additionTHF (10 mL) and sodium ethoxide (21% in EtOH, 4 mL) were added
  5. temperatureto cool
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe residue was dissolved in water
  8. additionthe pH was adjusted to <4 by addition of 4 N HCl
  9. filtrationThe precipitate was collected by filtration
  10. washwashed with water
  11. customdried on the funnel

出典と根拠

ORDレコード
ord-f15bdac829d74917a33560b0fcef7c35
出典データセット
uspto-grants-2014_01
特許番号
US08633207B2

関連ノート

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