2-(Piperidin-4-yl)-1,3-benzothiazole → alpha-(R)-(3-(S)-((4-(benzothiazol-2-yl)piperidin-1-yl)methyl)-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid, 4-methoxybenzyl ester

HRID 1068143노트

반응식

HRID 1068143 반응식
[CH:1]([C@@H:3]1[C@@H:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:6][N:5]([C@H:14]([CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)[C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)=[O:16])[CH2:4]1)=O.[NH:33]1[CH2:38][CH2:37][CH:36]([C:39]2[S:40][C:41]3[CH:47]=[CH:46][CH:45]=[CH:44][C:42]=3[N:43]=2)[CH2:35][CH2:34]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1>[S:40]1[C:41]2[CH:47]=[CH:46][CH:45]=[CH:44][C:42]=2[N:43]=[C:39]1[CH:36]1[CH2:35][CH2:34][N:33]([CH2:1][C@@H:3]2[C@@H:7]([C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH2:6][N:5]([C@H:14]([CH:27]3[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]3)[C:15]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)=[O:16])[CH2:4]2)[CH2:38][CH2:37]1

참가 물질

5

반응물 3

HCID 14774392-(Piperidin-4-yl)-1,3-benzothiazoleHCID 5049666Sodium triacetoxyborohydrideHCID 53654320alpha-(R)-(3-(R)-formyl-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid 4-methoxybenzyl ester

생성물 1

HCID 57100094alpha-(R)-(3-(S)-((4-(benzothiazol-2-yl)piperidin-1-yl)methyl)-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid, 4-methoxybenzyl ester수율 73.5%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of 52 mg of α-(R)-(3-(R)-formyl-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid, 4-methoxybenzyl ester (prepared above as Aldehyde 5) and 50 mg of 2-(piperidin-4-yl)benzothiazole (from Step B) in 2.5 mL of THF was added two spatula tips of 3 Å molecular sieves. After stirring at room temperature for 20 mim., 50 mg of sodium triacetoxyborohydride was added and the reaction was stirred at room temperature for 18 hours. The reaction was quenched with MeOH and diluted with EtOAc. After filtering molecular sieves, the filtrate was concentrated under reduced pressure. The residue was partitioned between EtOAc and water. The organic layer was washed with brine and dried over anhydrous MgSO4. Concentration under reduced pressure followed by flash chromatography eluting with 20% EtOAc in hexane followed by 50% EtOAc in hexane afforded 56 mg of the title compound as a white solid.

후처리

  1. stirringthe reaction was stirred at room temperature for 18 hours
  2. customThe reaction was quenched with MeOH
  3. additiondiluted with EtOAc
  4. filtrationAfter filtering molecular sieves
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe residue was partitioned between EtOAc and water
  7. washThe organic layer was washed with brine
  8. dry with materialdried over anhydrous MgSO4
  9. concentrationConcentration under reduced pressure
  10. washeluting with 20% EtOAc in hexane

출처 및 근거

ORD 기록
ord-9fc759afbf49490398c06cdb171b41b9
출처 데이터셋
uspto-grants-2001_06
특허 번호
US06248755B1

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