Methanol → 5-Amino-N-{4-[(3S,5R)-3-amino-5-(trifluoromethyl)piperidin-1-yl]-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl}-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide

HRID 1499515노트

반응식

HRID 1499515 반응식
C([O:4][CH:5]1[C:9]2=[N:10][CH:11]=[C:12]([NH:32][C:33]([C:35]3[N:36]=[C:37]([C:48]4[C:53]([F:54])=[CH:52][CH:51]=[CH:50][C:49]=4[F:55])[S:38][C:39]=3[NH:40]C(OC(C)(C)C)=O)=[O:34])[C:13]([N:14]3[CH2:19][C@H:18]([C:20]([F:23])([F:22])[F:21])[CH2:17][C@H:16]([NH:24]C(OC(C)(C)C)=O)[CH2:15]3)=[C:8]2[CH2:7][CH2:6]1)(=O)C.[OH-].[Na+].O.CO>C1COCC1>[NH2:40][C:39]1[S:38][C:37]([C:48]2[C:49]([F:55])=[CH:50][CH:51]=[CH:52][C:53]=2[F:54])=[N:36][C:35]=1[C:33]([NH:32][C:12]1[C:13]([N:14]2[CH2:19][C@H:18]([C:20]([F:22])([F:23])[F:21])[CH2:17][C@H:16]([NH2:24])[CH2:15]2)=[C:8]2[CH2:7][CH2:6][CH:5]([OH:4])[C:9]2=[N:10][CH:11]=1)=[O:34]

참가 물질

6

반응물 4

HCID 887MethanolHCID 962WaterHCID 14798Sodium HydroxideHCID 867267453-({[5-[(tert-Butoxycarbonyl)amino]-2-(2,6-difluorophenyl)-1,3-thiazol-4-yl]carbonyl}amino)-4-[(3S,5R)-3-[(tert-butoxycarbonyl)amino]-5-(trifluoromethyl)piperidin-1-yl]-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetate

생성물 1

HCID 867267465-Amino-N-{4-[(3S,5R)-3-amino-5-(trifluoromethyl)piperidin-1-yl]-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl}-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide수율 24%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of 3-({[5-[(tert-butoxycarbonyl)amino]-2-(2,6-difluorophenyl)-1,3-thiazol-4-yl]carbonyl}amino)-4-[(3S,5R)-3-[(tert-butoxycarbonyl)amino]-5-(trifluoromethyl)piperidin-1-yl]-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetate (110.3 mg, 0.1384 mmol) in THF (1.0 mL) was added a 1.0 M NaOH solution in water (1.00 mL, 1.00 mmol) followed by MeOH (2.0 mL). The reaction mixture was stirred at room temperature for 1 h, and then concentrated under reduced pressure. To the resulting residue was added DCM (2.0 mL), followed by TFA (2.0 mL). The mixture was stirred at room temperature for 30 min., and then concentrated under reduced pressure. The resulting residue was purified using RP-HPLC (XBridge™ C18 column, eluting with a gradient of MeCN/water containing 0.1% NH4OH, at flow rate of 30 mL/min.) to afford both diastereoisomers of the title compound as white solids (9.3 mg for each, total yield 24%).

후처리

  1. concentrationconcentrated under reduced pressure
  2. additionTo the resulting residue was added DCM (2.0 mL)
  3. stirringThe mixture was stirred at room temperature for 30 min.
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified
  6. washeluting with a gradient of MeCN/water containing 0.1% NH4OH, at flow rate of 30 mL/min.)

출처 및 근거

ORD 기록
ord-997d97c75a5c42b9b9acdc0bfcd9087f
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09200004B2

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