Diisopropyl Ether → N-Boc-sitagliptin

HRID 590632

반응식

HRID 590632 반응식
[C:1]([O:5][C:6]([NH:8][CH:9]([CH2:14][C:15]1[CH:20]=[C:19]([F:21])[C:18]([F:22])=[CH:17][C:16]=1[F:23])[CH2:10][C:11]([OH:13])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.Cl.[F:34][C:35]([F:46])([F:45])[C:36]1[N:40]2[CH2:41][CH2:42][NH:43][CH2:44][C:39]2=[N:38][N:37]=1.ClC1C=CC=CC=1B(O)O.C(OC(C)C)(C)C>O.C1(C)C=CC=CC=1>[C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:9]([CH2:10][C:11](=[O:13])[N:43]1[CH2:42][CH2:41][N:40]2[C:36]([C:35]([F:46])([F:34])[F:45])=[N:37][N:38]=[C:39]2[CH2:44]1)[CH2:14][C:15]1[CH:20]=[C:19]([F:21])[C:18]([F:22])=[CH:17][C:16]=1[F:23])([CH3:2])([CH3:3])[CH3:4]

참가 물질

8

반응물 5

HCID 7914Diisopropyl EtherHCID 81531DiisopropylethylamineHCID 27343222-Chlorophenylboronic acidHCID 119613713-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochlorideHCID 21911205Boc-(R)-3-Amino-4-(2,4,5-trifluoro-phenyl)-butyric acid

생성물 1

HCID 46836576N-Boc-sitagliptin

시약·촉매·용매 2

HCID 962Water용매HCID 1140Toluene용매

실험 절차

25 g of 3-tert-butoxycarbonylamino-4-(2,4,5-trifluorophenyl)butyric acid of formula (II) was charged with 200 ml of toluene into a 500 ml 4 necked round bottom flask attached with dean stark apparatus, followed by the addition of 25 ml of Hunig's base at room temperature. Then 25 g of 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine HCl was charged and stirred for 5 minutes. 11.5 g of 2-chloro phenyl boronic acid was charged to the reaction mass. After 48 hours of stirring at reflux temperature, the reaction was complete. The reaction mass was cooled to room temperature and 250 ml of water was added to it. The organic layer was separated and washed twice with 125 ml of 1N HCl. The organic layer was separated and washed with 125 ml of water followed by 6% NaHCO3 and finally by 125 ml of water. The organic layer was then separated and the solvent was distilled out under vacuum. The solid obtained was stirred with 125 ml of diisopropyl ether for 2 hours, filtered and then dried under vacuum at 50° C. for 12-15 hours. HPLC was used to obtain the chromatographic purity and chiral purity.

후처리

  1. stirringAfter 48 hours of stirring
  2. temperatureat reflux temperature
  3. customThe organic layer was separated
  4. washwashed twice with 125 ml of 1N HCl
  5. customThe organic layer was separated
  6. washwashed with 125 ml of water
  7. customThe organic layer was then separated
  8. distillationthe solvent was distilled out under vacuum
  9. customThe solid obtained
  10. filtrationfiltered
  11. customdried under vacuum at 50° C. for 12-15 hours
  12. customto obtain the chromatographic purity and chiral purity

출처 및 근거

ORD 기록
ord-1db69670f5dd45a996e5fe2b6f0b6014
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09233967B2

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